Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science

Advancements in Transdermal Drug Delivery

Description

This cluster of papers focuses on innovations in transdermal drug delivery systems, including the use of solid lipid nanoparticles, microneedles, skin penetration enhancers, nanostructured lipid carriers, and microemulsion-based drug delivery. It explores advancements in overcoming the skin's barrier function and enhancing skin permeation for effective drug delivery.

Keywords

Solid Lipid Nanoparticles; Microneedles; Skin Penetration Enhancers; Nanostructured Lipid Carriers; Transdermal Drug Delivery; Skin Barrier Function; Microemulsion-based Drug Delivery; Iontophoretic Drug Delivery; Skin Permeation Enhancement; Stratum Corneum

Based on recent morphologic, histochemical, and biochemical data, we propose a heterogeneous two-compartment model of the stratum corneum that ascribes a special role for intercellular lipids in the regulation of … Based on recent morphologic, histochemical, and biochemical data, we propose a heterogeneous two-compartment model of the stratum corneum that ascribes a special role for intercellular lipids in the regulation of stratum corneum barrier function and desquamation. The evidence in favor of the model and several predictions based on the model are surveyed in this review.
Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of … Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon γ, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.
Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other … Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their advantages, limitations and their possible remedies. The different types of nanocarriers which were based on solid lipid like solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugates are discussed with their structural differences. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases.
Significance For exploiting synthetic glucose-responsive insulin delivery systems, challenges remain to demonstrate a strategy that would combine ( i ) fast responsiveness, ( ii ) ease of administration, and ( … Significance For exploiting synthetic glucose-responsive insulin delivery systems, challenges remain to demonstrate a strategy that would combine ( i ) fast responsiveness, ( ii ) ease of administration, and ( iii ) excellent biocompatibility. We have developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing hypoxia-sensitive hyaluronic acid-based vesicles. The vesicles quickly dissociate and release encapsulated insulin under the local hypoxic environment, caused by the enzymatic oxidation of glucose in the hyperglycemic state. This ā€œsmart insulin patchā€ with a new enzyme-based glucose-responsive mechanism can regulate the blood glucose of type 1 diabetic mice to achieve normal levels, with faster responsiveness compared with the commonly used pH-sensitive formulations, and can avoid the risk of hypoglycemia.
Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable … Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo , including microinjection of insulin to reduce blood glucose levels in diabetic rats.
Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing … Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and bioavailability. Furthermore, they show an unlimited capacity in the field of drug targeting. The properties of nano-medicines such as release from dosage forms at specific sites as well as drug circulation and absorption into body membranes are dramatically affected by some physical and chemical characteristics of nano-drugs. Particle size and charge are two major factors which could play key roles in this regard. In this paper, the effect of zeta potential on different properties of nano-drug delivery systems is reviewed.Keywords: Nano-drug delivery, Zeta potential, Drug targeting, Particle size, Particle charge
ABSTRACT: Over the past decade, great progress has been made toward elucidating the structure and function of the stratum corneum (SC), the outermost layer of the epidermis. SC cells (corneocytes) … ABSTRACT: Over the past decade, great progress has been made toward elucidating the structure and function of the stratum corneum (SC), the outermost layer of the epidermis. SC cells (corneocytes) protect against desiccation and environmental challenge by regulating water flux and retention. Maintenance of an optimal level of hydration by the SC is largely dependent on several factors. First, intercellular lamellar lipids, organized predominantly in an orthorhombic gel phase, provide an effective barrier to the passage of water through the tissue. Secondly, the diffusion path length also retards water loss, since water must traverse the tortuous path created by the SC layers and corneocyte envelopes. Thirdly, and equally important, is natural moisturizing factor (NMF), a complex mixture of low-molecular-weight, water-soluble compounds first formed within the corneocytes by degradation of the histidine-rich protein known as filaggrin. Each maturation step leading to the formation of an effective moisture barrier—including corneocyte strengthening, lipid processing, and NMF generation—is influenced by the level of SC hydration. These processes, as well as the final step of corneodesmolysis that mediates exfoliation, are often disturbed upon environmental challenge, resulting in dry, flaky skin conditions. The present paper reviews our current understanding of the biology of the SC, particularly its homeostatic mechanisms of hydration.
The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of … The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.
Abstract The penetration of drugs and other micromolecules through intact human skin can be regarded as a process of dissolution and molecular diffusion through a composite, multilayer membrane, whose principal … Abstract The penetration of drugs and other micromolecules through intact human skin can be regarded as a process of dissolution and molecular diffusion through a composite, multilayer membrane, whose principal barrier to transport is localized within the stratum corneum. A mathematical model of the stratum corneum as a two‐phase protein‐lipid heterogeneous membrane (in which the lipid phase is continuous) correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid‐protein partition coefficient. Experimentally measured permeabilities of human skin to a variety of drugs have been found to conform to this model. The extraordinarily low permeability of skin to most micromolecules appears to arise from the very low diffusivity of such molecules in the intercellular lipid phase.
Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed … Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs.
Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and … Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Microneedles have been extensively investigated in recent decades for drug and vaccine delivery as well as minimally invasive patient monitoring/diagnosis. This review focuses on a range of critically important aspects of microneedle technology, namely their material composition, manufacturing techniques, methods of evaluation and commercial translation to the clinic for patient benefit and economic return. Microneedle research and development is finally now at the stage where commercialisation is a realistic possibility. However, progress is still required in the areas of scaled-up manufacture and regulatory approval.
Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and … Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.
During the recent years, more attentions have been focused on lipid base drug delivery system to overcome some limitations of conventional formulations. Among these delivery systems solid lipid nanoparticles (SLNs) … During the recent years, more attentions have been focused on lipid base drug delivery system to overcome some limitations of conventional formulations. Among these delivery systems solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems due to the ease of manufacturing processes, scale up capability, biocompatibility, and also biodegradability of formulation constituents and many other advantages which could be related to specific route of administration or nature of the materials are to be loaded to these delivery systems. The aim of this article is to review the advantages and limitations of these delivery systems based on the route of administration and to emphasis the effectiveness of such formulations.
The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due … The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.
Microneedle technology has emerged as a promising approach for drug delivery, vaccination, diagnostics, and cosmetic treatments. This review provides an overview of microneedle technology, covering the various types of microneedles, … Microneedle technology has emerged as a promising approach for drug delivery, vaccination, diagnostics, and cosmetic treatments. This review provides an overview of microneedle technology, covering the various types of microneedles, fabrication techniques, applications, advantages, challenges, safety considerations, clinical translation, and future perspectives. Solid, hollow, dissolving, coated, and hydrogel-forming microneedles are discussed, along with their structures, materials, and fabrication methods. Applications in drug delivery, vaccination, diagnostics, and cosmetic treatments are explored, with an emphasis on emerging and novel uses. The review highlights the advantages of microneedle technology, including enhanced patient compliance, improved drug absorption, and reduced pain, as well as challenges such as manufacturing scalability and regulatory approval. Fabrication techniques, biocompatibility, safety issues, clinical translation, and commercialization aspects are examined, along with future directions and emerging trends such as multifunctional microneedles and personalized medicine. Overall, microneedle technology holds tremendous promise for revolutionizing healthcare and biomedical engineering, but further research and development are required to address current challenges and realize its full potential.
Neuropathic pain is a complex and debilitating condition that presents substantial challenges for effective treatment, as it often persists despite conventional therapies and can significantly impair the quality of life … Neuropathic pain is a complex and debilitating condition that presents substantial challenges for effective treatment, as it often persists despite conventional therapies and can significantly impair the quality of life of affected individuals. Currently, pregabalin is the first-line treatment for neuropathic pain. However, its oral dosage form is often associated with adverse reactions such as dizziness and drowsiness, and its administration duration is limited, requiring frequent dosing. To address these issues, this study developed a hyaluronic acid (HA)-based dissolving microneedle (MN) patch incorporating poly (lactic-co-glycolic acid) (PLGA) microspheres (MS) loaded with pregabalin (PG) for peripheral administration. The MN array consists of 10 Ɨ 10 needles, covering an area of ā‰ˆ0.5 cm2, with each needle having a height of 850 µm. The MN patch demonstrated significant analgesic effects and sustained drug release at the application site for up to 48 h, effectively alleviating pain while minimizing dizziness and drowsiness, which are the most common side effects after systemic administration. This innovative MN platform presents a promising strategy for neuropathic pain management and provides a novel therapeutic paradigm for the peripheral application of centrally acting analgesics.
<title>Abstract</title> <bold>Purpose:</bold> The study was undertaken to formulate and evaluate a nanoemulgel of Flufenamic acid to enhance its topical delivery. Flufenamic acid, a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID), suffers … <title>Abstract</title> <bold>Purpose:</bold> The study was undertaken to formulate and evaluate a nanoemulgel of Flufenamic acid to enhance its topical delivery. Flufenamic acid, a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID), suffers from limited skin penetration and therapeutic efficacy in conventional formulations. The aim was to improve its solubility, stability, and anti-inflammatory activity using a nanoemulgel system. <bold>Methods:</bold> A nanoemulsion was developed using clove oil as the oil phase, Tween 80 as surfactant, and PEG 200 as co-surfactant by spontaneous emulsification and sonication. The optimized nanoemulsion was then incorporated into a Carbopol 940 gel base to obtain the nanoemulgel. The formulation was evaluated for physicochemical properties such as droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, drug content, spreadability, and extrudability. <italic>In vitro</italic> drug release was studied using Franz diffusion cell, and anti-inflammatory activity was assessed by protein denaturation method. <bold>Results:</bold> The optimized nanoemulgel exhibited a droplet size of 118.4 nm, zeta potential of āˆ’22.2 mV, and entrapment efficiency of 97.72%. Drug release studies showed a sustained release profile with 78.22% cumulative release over 12 hours, compared to 97.71% for conventional gel. <italic>In vitro</italic> anti-inflammatory activity demonstrated 90.90 %,80.30% and 71.21 % inhibition at 1000 μg/mL, of pure drug, nanoemulgel, and marketed gel <bold>Conclusion:</bold> The formulated nanoemulgel significantly enhanced topical delivery of Flufenamic acid by improving solubility, stability, and sustained drug release. It provides an effective approach for enhancing topical delivery of poorly water-soluble drug.
Abstract Background Abnormal scarring and fibrotic skin disorders arise from dysregulated wound healing processes. While Aloe vera is widely recognized for its therapeutic properties, the potential of its extracellular vesicles … Abstract Background Abnormal scarring and fibrotic skin disorders arise from dysregulated wound healing processes. While Aloe vera is widely recognized for its therapeutic properties, the potential of its extracellular vesicles (Av-EVs) remains underexplored. Objective This study aimed to isolate and characterize Av-EVs and evaluate their antioxidant, anti-inflammatory, and antifibrotic properties in vitro , focusing on the impact of extraction method and plant maturity. Methods Av-EVs were isolated from mature Aloe vera leaves using manual (NB) or blender-based (B) homogenization. Vesicles were characterized by nanoparticle tracking analysis, transmission electron microscopy, and protein quantification. Antioxidant and cytotoxicity assays (DPPH, alamarBlue) were followed by functional anti-inflammatory and antifibrotic analyses respectively in LPS-stimulated THP-1 macrophages and TGF-β1/Vitamin C-activated human dermal fibroblasts (RT-qPCR, immunofluorescence). Results NB-derived EVs from mature leaves exhibited the most potent activity across all assays, showing superior antioxidant capacity, greater suppression of pro-inflammatory cytokines, enhanced M2/M2a macrophage polarization, and significant downregulation of COL1A1 and α-SMA. In contrast, B-derived and young leaf-derived EVs showed reduced bioactivity, with young EVs failing to inhibit fibrotic markers. Conclusion Manually extracted Av-EVs from mature leaves demonstrate superior multifunctional bioactivity, highlighting their potential as plant-derived nanotherapeutics for fibrotic scar modulation.
Bacterial infectious stomatitis (BIS), characterized by severe infections overlaying ulcers, poses complex therapeutic challenges and often results in prolonged healing, leading to significant patient discomfort. To address this clinical challenge, … Bacterial infectious stomatitis (BIS), characterized by severe infections overlaying ulcers, poses complex therapeutic challenges and often results in prolonged healing, leading to significant patient discomfort. To address this clinical challenge, a biomimetic microneedle (MN) suction cup is designed inspired by the tarsal claw of Drosophila. The suction cup component is crafted from polyvinyl alcohol (PVA) hydrogel, while the MN section, embedded within the suction cup, comprises a thermoresponsive and antibacterial composite hydrogel infused with the drug S-nitrosoglutathione (GSNO). This innovative design not only ensures strong adhesion to moist surfaces but also provides substantial antibacterial and anti-inflammatory effects, controlled drug release, active promotion of concentric wound contraction, and enhanced vasodilation, thereby facilitating rapid and comprehensive healing of BIS. The multifunctionality of the MN suction cup patch developed in this study represents a significant innovation over traditional treatment methods and holds potential for widespread application in dental clinics.
The present study aimed to develop and optimise Ranolazine-loaded Nanostructured Lipid Carriers (RNZ-NLCs) to overcome the poor oral bioavailability and rapid clearance associated with Ranolazine, thereby improving its therapeutic efficacy. … The present study aimed to develop and optimise Ranolazine-loaded Nanostructured Lipid Carriers (RNZ-NLCs) to overcome the poor oral bioavailability and rapid clearance associated with Ranolazine, thereby improving its therapeutic efficacy. RNZ-NLCs were prepared using the hot high-pressure homogenisation technique and optimised using a 2³ factorial design. Characterisation techniques included dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infra-red spectroscopy (FTIR), in vitro drug release profiling, and pharmacokinetic analysis in rats. The optimised RNZ-NLCs exhibited a mean diameter of 205.8 nm, a polydispersity index (PDI) of 0.318, a surface charge (Zeta potential) of -22.4 mV and drug loading of 8.01% w/w. DSC and XRD studies confirmed the transformation of Ranolazine into an amorphous state, and FTIR indicated no chemical interaction with excipients. In vitro release studies showed a sustained release profile, with 65% drug release at 12 hours and 90% at 24 hours, fitting the Korsmeyer-Peppas model. Long-term storage stability studies over 90 days revealed no significant changes in particle characteristics. Pharmacokinetic evaluation in rats showed that RNZ-NLCs increased the Cmax to 18.621 µg/mL (from 9.413 µg/mL for free RNZ), delayed Tmax to 4 h (from 2 h), and enhanced AUC0-āˆž to 217.02 µgĀ·h/mL (from 32.06 µgĀ·h/mL). Additionally, mean residence time (MRT) and elimination half-life (t1/2) were extended to 11.83 h and 6.81 h, respectively. RNZ-NLCs significantly improved the pharmacokinetic profile and storage stability of Ranolazine, indicating their potential as a promising delivery system for enhancing oral bioavailability and therapeutic efficacy.
This study emphasizes developing a microsponge-based delivery system for propylparaben, a broadly used preservative in skin creams. The microsponge technology was employed to control the release of propylparaben, thereby reducing … This study emphasizes developing a microsponge-based delivery system for propylparaben, a broadly used preservative in skin creams. The microsponge technology was employed to control the release of propylparaben, thereby reducing the risk of skin irritation and other adverse effects. The optimized microsponge formulation was incorporated into a cold cream and evaluated for its physical properties, in vitro release profile, and preservative efficacy. The results reveal that the microsponge-loaded propyl paraben provided sustained release and improved preservative activity, ultimately extending the shelf life of the cold cream. This innovative formulation offers a promising approach to enhancing the safety and effectiveness of skin creams. Particle size analysis showed that as the amount of polymer in the formulation increased, the particle size range of the batches also grew. Differential Scanning Calorimetry studies of the pure drug, ethyl cellulose, and propyl paraben-loaded microsponges revealed no interactions between the drug and the excipients. Similarly, Infrared spectroscopy analysis confirmed the absence of any interactions. Antimicrobial preservative testing conducted in a microbiology lab revealed the diameter of the zone of inhibition for the prepared microsponges, cold cream with the microsponges, and plain cream, demonstrating the antimicrobial potential of the microsponge-based formulation.
Transdermal microneedle systems have received great attention due to their minimally invasive way of delivering biomolecules through the skin with reduced pain. However, designing high-strength separable microneedles, which enable easy … Transdermal microneedle systems have received great attention due to their minimally invasive way of delivering biomolecules through the skin with reduced pain. However, designing high-strength separable microneedles, which enable easy skin penetration and easy patch detachment, is challenging. Here, we present a Parametric Rule-based Intelligent System (PRISM), which generates the design of and analyzes high-strength separable microneedles. The PRISM platform integrates parametric 3D modeling, geometry-based structural analysis, and high-resolution micro-3D printing for the creation of high-strength separable microneedles. We fabricated prototype microneedle arrays via microscale stereolithographic printing (pµSL) and demonstrated separation of microneedle tips in a skin-mimicking phantom sample. Mechanical testing showed that the suggested design achieved 2.13 ± 0.51 N axial resistance and 73.92 ± 34.77 mN shear fracture force; this surpasses that of conventional designs. Finally, an experiment using a skin-mimicking artificial phantom sample confirmed that only the PRISM-designed separable microneedles could have been inserted and separated at the target depth, whereas conventional designs failed to detach. This approach addresses the development of microneedle systems, which achieve both robust skin phantom penetration and reliable separable delivery, presenting an efficient development tool in transdermal drug delivery technology.
The present work aims to comprehensively examine and analyze Niosomal formulations, with a special focus on their potential use as a targeted delivery approach for the treatment of breast cancer. … The present work aims to comprehensively examine and analyze Niosomal formulations, with a special focus on their potential use as a targeted delivery approach for the treatment of breast cancer. The objective of this study is to get in-depth understanding of the dynamic field of cancer therapeutics by conducting a thorough examination of formulation parameters and characterization techniques. The research aims to address the pressing need for novel treatment options in light of breast cancer's increasing prevalence and impact on women's health in India. This disease has now surpassed cervical cancer as a major cause of morbidity and death among women in the country. Niosomes, which are vesicles composed of lipids, have shown the capacity to augment the sustained release of drugs, so enabling a controlled and prolonged therapeutic effect. By using the mechanism of endocytosis, these formulations effectively promote the internalization of medicines into cellular structures, so permitting precise delivery to specific intracellular locations. The investigation of niosomal formulations as precise delivery methods in the context of breast cancer treatment signifies a notable development in the field of cancer therapies. Niosomes has distinctive characteristics that render them very promising vehicles for drug delivery, since they have the capacity to be customized for precise targeting of cancer cells while minimizing detrimental impacts on healthy organs. Therefore, the use of niosomal formulations as a precise delivery strategy in the treatment of breast cancer has potential in enhancing the therapeutic efficacy of anticancer medications while mitigating undesired adverse reactions. Ongoing scholarly research activities are focused on further investigating and improving these formulations, with the objective of maximizing their efficacy in clinical environments.
Viral infections such as herpes simplex virus (HSV), human papillomavirus (HPV), and others present a significant global health challenge due to their recurrent nature and limited treatment options. Topical antiviral … Viral infections such as herpes simplex virus (HSV), human papillomavirus (HPV), and others present a significant global health challenge due to their recurrent nature and limited treatment options. Topical antiviral therapy offers a targeted and patient-compliant approach to manage localized infections, with reduced systemic side effects. However, the skin’s barrier—particularly the stratum corneum—poses a major obstacle to effective drug delivery. This review highlights the advances in topical antiviral therapy with a special emphasis on liposomal nanocarriers, which have emerged as promising vehicles for enhancing drug penetration, stability, and localized action. Liposomes, owing to their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs, improve the bioavailability of conventional and herbal antiviral agents. Furthermore, the synergistic potential of combining synthetic antivirals like acyclovir with phytochemicals such as curcumin enhances therapeutic outcomes while minimizing resistance and toxicity. The paper also discusses formulation strategies such as use of penetration enhancers, hydrogel systems, and deformable liposomes (e.g., ethosomes, transfersomes), as well as physical enhancement techniques like microneedles. Overall, nanocarrier-based topical therapies represent a transformative direction in antiviral treatment, offering controlled release, improved efficacy, and better patient adherence.
Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing … Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer-Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC50 of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.
Miki Wada , Kazuhiro Shiga , Toshihiro Mori +1 more | Journal of Society of Cosmetic Chemists of Japan
Deep vein thrombosis (DVT) is the third major leading cause of mortality and morbidity after cardiovascular disease and stroke. Cilostazol (CLZ) being one of the antiplatelet agents is effectively used … Deep vein thrombosis (DVT) is the third major leading cause of mortality and morbidity after cardiovascular disease and stroke. Cilostazol (CLZ) being one of the antiplatelet agents is effectively used in DVT. However, its oral administration is associated with several problems, such as gastrointestinal side effects and extensive first-pass metabolism. Herein, CLZ-loaded transethosomes (CLZ-TEs) were prepared and incorporated in chitosan gel (CLZ-TEG) for transdermal administration. Box-Behnken Design ExpertĀ® software was used to statistically optimize CLZ-TEs. Particle properties, Transmission electron microscopy (TEM) and Fourier Transform Infrared spectroscopy (FTIR) analyses of CLZ-TEs were accomplished followed by in vitro release and permeation studies and its comparison with CLZ-TEG, CLZ-dispersion (Ds) and CLZ-G. Moreover, skin irritation and pharmacokinetics studies of the optimized CLZ-TEG were executed. The optimized CLZ-TEs showed a mean particle size of 174 nm, polydispersity index of 0.173, zeta potential of -30 mV and entrapment efficiency of 99%. TEM exhibited spherical nanovesicles and FTIR demonstrated compatibility of the excipients. Moreover, CLZ-TEG was homogeneous, smooth, and spreadable. Similarly, CLZ-TEG displayed sustained release and enhanced permeation of the CLZ. Furthermore, pharmacokinetic study showed significantly improved (p < 0.05) bioavailability of CLZ-TEG when compared with CLZ-G and CLZ-Ds. It was concluded that CLZ-TEG may be a potential candidate for the management of DVT.
The nanoencapsulation of buriti oil enhances skin coverage and potentiates its antioxidant and wound-healing activities by protecting bioactive compounds and improving topical application. This study aimed to optimize nanocapsule formulations … The nanoencapsulation of buriti oil enhances skin coverage and potentiates its antioxidant and wound-healing activities by protecting bioactive compounds and improving topical application. This study aimed to optimize nanocapsule formulations through experimental design. A full 2³ factorial design was employed, varying the concentrations of surfactant (0.15 to 0.75 g), polymer, and buriti oil, generating 18 formulations. Nanocapsules were prepared by interfacial polymer deposition and characterized by dynamic light scattering and electrophoretic mobility to determine mean diameter, polydispersity index (PDI), and zeta potential. Formulations that exhibited phase separation typically contained higher amounts of oil and surfactant. The second-order polynomial model best described the effects of formulation variables. Surfactant and oil content significantly influenced particle size, while zeta potential remained largely unaffected by the independent variables. Lower surfactant concentration (0.15 g) led to larger particle diameters but increased homogeneity, as shown by PDI. Higher surfactant amounts (0.75 g) reduced diameter but did not always prevent phase separation in formulations with more oil. Zeta potential results varied irregularly, indicating limited influence of polymer and surfactant concentration. These findings underscore the importance of optimizing surfactant and oil levels to achieve stable nanocapsules with desirable characteristics. Experimental design proved effective in identifying relevant formulation parameters and can guide future improvements in nanoformulations for dermocosmetic applications.
Introduction Several complex mathematical models have been developed using in vitro permeation test [IVPT) data to characterize percutaneous absorption. A less complicated approach, using basic pharmacokinetic parameters on IVPT data, … Introduction Several complex mathematical models have been developed using in vitro permeation test [IVPT) data to characterize percutaneous absorption. A less complicated approach, using basic pharmacokinetic parameters on IVPT data, is proposed here to predict skin barrier content and permeation kinetics following multiple dose applications. Methods Published and archived data from the authors’ files is used to define and test a proposed model using standard single compartment pharmacokinetic parameters, and to provide insight into percutaneous absorption profiles and skin barrier content. Results Pharmacokinetic parameters are derived and shown for a selection of diverse drugs from their IVPT data, which are then used to predict multiple-dose absorption kinetics. Flux profiles and skin barrier content are calculated and shown for periods of 7-30 days with 6, 12 and 24 hr dosing intervals. Conclusion The model presented here, allows one to predict the rate and extent of drug absorption over any number of dosing periods per day, and across multiple days. This information may not only provide a new outlook on formulation selection or dosing regimens, but may also allow for estimation of skin or systemic levels of exposure to chemicals following multiple sequential topical dose applications.
Abstract Background Understanding the physiological and biophysical characteristics of skin provides information for developing appropriate management strategies for skin diseases. However, in dogs, variations in skin biophysical parameters, such as … Abstract Background Understanding the physiological and biophysical characteristics of skin provides information for developing appropriate management strategies for skin diseases. However, in dogs, variations in skin biophysical parameters, such as age, sex and breed, remain poorly understood. Hypothesis/Objectives This study analysed three biophysical characteristics of healthy dog skin (hydration, pH and sebum content) and investigated the effects of sex, age and breed. Materials and Methods One hundred forty‐nine dogs without skin problems were enrolled. Skin hydration, pH and sebum content were measured using a multifunctional skin physiology monitor. The dogs were divided into four age groups: &lt;1 year, 1–6 years, 7–12 years and &gt;13 years. Results Skin hydration levels were significantly lower in the &gt;13 years group than in the 1–6 years and 7–12 groups. Additionally, skin pH levels in the &gt;13 years group were significantly lower than in the 7–12 group. Furthermore, skin biophysical parameters among the five breed groups – beagles (n = 37), Malteses (n = 18), miniature poodles (n = 24), cocker spaniels (n = 11) and Pomeranians (n = 12) – revealed that skin hydration and pH were significantly higher in beagles than those of Malteses and miniature poodles. Conclusions and Clinical Relevance These findings indicate that biophysical properties, including skin hydration and pH, vary with age and breed. This study provides fundamental data on the effects of age, sex and breed on the biophysical characteristics of dog skin.
To reduce the overuse of antibiotics, on-demand antibiotic administration guided by rapid infection assessment is of particular importance. In this study, we present a portable, multifunctional hydrogel microneedle (MN) woundplast … To reduce the overuse of antibiotics, on-demand antibiotic administration guided by rapid infection assessment is of particular importance. In this study, we present a portable, multifunctional hydrogel microneedle (MN) woundplast capable of real-time monitoring of wound adenosine triphosphate (ATP) levels and simultaneous antibacterial therapy. By leveraging the aggregation-induced emission effect, metal-organic frameworks (MOFs) coencapsulating gold nanoclusters (AuNCs) and vancomycin are integrated into the MN tips, where ATP-Zn2+ interactions enable selective ATP recognition and quantification across 0-5 mM. The MN incorporates therapeutic logic, utilizing ATP as a pathological marker to determine the drug release kinetics within the wound microenvironment. In this process, the synergistic effect of Zn2+ and vancomycin played an important role in achieving superior bactericidal efficacy. Moreover, the positively charged MN surface demonstrated 2.4-fold higher bacterial adsorption than neutral counterparts. In vivo experiments demonstrated that this platform both monitored infected wounds and accelerated healing, reducing wound areas to 26.6% of the control group while achieving recovery rates equivalent to noninfected conditions. This ATP-guided therapeutic platform provides a closed-loop strategy for combating antibiotic resistance in wound management.
Abstract The safety of repeated microarray patch (MAP) application is crucial for its development as an innovative drug delivery platform. This study is the first to assess the safety of … Abstract The safety of repeated microarray patch (MAP) application is crucial for its development as an innovative drug delivery platform. This study is the first to assess the safety of repeated applications of hydrogel‐forming, dissolving, and implantable MAPs over four weeks using miniature pigs, an industry‐standard dermatological model with human‐like skin structure and physiological responses. Uniform MAPs are successfully manufactured, with application forces of 32 N/array resulting in less than 15% needle height reduction. ā‰ˆ80% of the needle length penetrated Parafilm layers, while 40–60% penetrated excised porcine skin. Repeated MAP applications do not compromise skin barrier function, as confirmed by transepidermal water loss measurements, and caused no adverse skin reactions per modified Draize test results. Systemic safety assessments revealed no significant immune responses, allergic reactions, infections, or inflammatory markers (TNF‐α, IgE, IgG, CRP, and IL‐1β) between day 0 and day 28. No weight loss, infection signs, kidney toxicity, or clinically relevant hematological or biochemical changes are observed. Histopathological evaluations confirmed the absence of lesions or adverse effects. These findings establish the safety of repeated hydrogel‐forming, dissolving, and implantable MAP applications, supporting their potential for safe, effective drug delivery and facilitating their translation from preclinical models to human clinical trials.
Developing a promising on-demand controllable microneedle drug delivery system could provide stronger self-control and precision delivery of a large payload capacity. Nevertheless, the efficacy of existing systems has been constrained … Developing a promising on-demand controllable microneedle drug delivery system could provide stronger self-control and precision delivery of a large payload capacity. Nevertheless, the efficacy of existing systems has been constrained by limitations in the therapeutic payload capacity and slow diffusion of molecules, as well as the necessity for external resource configurations. Drawing inspiration from the multidimensional biomimetic strategies observed in the material properties and functional mechanisms of the bombardier beetle's defensive secretion system, a battery-free and self-propelled biomimetic microneedle system (BSBMs) is proposed for improving therapeutic outcomes and enabling controlled, on-demand drug delivery. The self-powered microneedle delivery platform fully emulates the structure and spray mechanism of bombardier, employing Pt nanoparticles and H2O2 loaded in the reaction chamber, as a built-in fuel source for active and controllable payload delivery. The robust bionic gas injector can serve as an active engine, facilitating the effective permeation of drugs through hollow microneedles without a complex pumping system. This BSBMs triggers the H2O2 decomposition reaction through thumb pressure, generating O2 pressure as an endogenous driving force to achieve transdermally precise and on-demand drug delivery. The pharmacokinetics of drug release from the BSBMs were evaluated in vivo by quantifying the levels of levonorgestrel (LNG). This active delivery system maintains in vivo LNG concentrations within the therapeutic window range, greatly enhancing on-demand, controlled, and stable drug delivery. This versatile and efficient self-propelled bionic microneedle delivery technology holds substantial promise for a broad spectrum of transdermal therapeutic applications, offering a simplified, convenient, and improved method of administration.
Abstract An evaporation study was conducted on the skin of several volunteers to examine whether skin properties influence fragrance molecules’ evaporation rates. The aim was to identify the observed variations … Abstract An evaporation study was conducted on the skin of several volunteers to examine whether skin properties influence fragrance molecules’ evaporation rates. The aim was to identify the observed variations and explore the responsible fragrance molecular and skin factors. To study the evaporation phenomenon, fragrance molecules evaporation was semi‐quantified from each volunteer's skin. This approach allowed a comparison of evaporation across individuals and provided insights into how the fragrance molecules interacted differently depending on skin types. Skin properties were subsequently measured to explain the observed differences in evaporation between individuals. Statistical analysis was performed to understand how both skin type and the intrinsic properties of fragrance molecules contribute to the observed variations in evaporation rates. This study offers promising results, advancing our understanding of the evaporation behaviour of fragrance molecules and its relationship with the physicochemical properties of the skin and the intrinsic characteristics of the fragrances.
Abstract Objective The aim of the present study was to develop a cosmetic bioadhesive emulgel to incorporate niacinamide (NMD), based on the combination of sodium hyaluronate and carbomer, using the … Abstract Objective The aim of the present study was to develop a cosmetic bioadhesive emulgel to incorporate niacinamide (NMD), based on the combination of sodium hyaluronate and carbomer, using the Quality by Design (QbD) approach. Methods It was decided to design first a bioadhesive vehicle and after selecting the best formulation, to load the NMD into the optimized final emulgel. The potential interaction reported in the literature between the selected bioadhesive polymers was investigated by Fourier transform infrared spectroscopy and Raman confocal microscopy. The effect of formulation variables on quality attributes (phase separation by mechanical stress, adhesion, viscosity and spreadability) of the emulgels was studied. Response‐surface methodology was applied to optimize the formulation. After optimization, the final NMD emulgel was further characterized by rheometry assay, and ex vivo bioadhesion properties and skin absorption of NMD using human skin. Results No relevant interaction between both bioadhesive polymers at the working conditions was found. Emulgel formulations were physically stable, showed uniform spreadability and appropriate viscosity and detachment force values. A high percentage of the dosage of NMD in the optimized emulgel was accumulated between the skin surface and its upper layers over 24 h. In addition, no evidence of permeation through the full skin was found, which complied with the desired low systemic distribution. Conclusions NMD was successfully vehiculized in a bioadhesive emulgel developed using the QbD approach. No significant changes in the critical quality attributes of the bioadhesive vehicle were observed after the incorporation of the active ingredient. The product, designed to present an increased residence time on the application site, provides a time frame to facilitate its performance, enabling the active ingredient to remain accumulated between the skin surface and its upper layers. Finally, and most importantly, QbD, a time‐and cost‐saving development approach that leads to high‐quality products, proved to be an invaluable tool in this scientifically driven cosmetic project.
A series of hydrogels containing sodium alginate at different concentrations (2%, 3%, and 4%) and egg white were prepared through ionic cross-linking with calcium chloride (CaCl2) to obtain composite dressing … A series of hydrogels containing sodium alginate at different concentrations (2%, 3%, and 4%) and egg white were prepared through ionic cross-linking with calcium chloride (CaCl2) to obtain composite dressing materials. ZnO nanoparticles coated with eucalyptus or lavender essential oil were introduced into the hydrogel matrix to enhance antibacterial properties. The resulting hydrogels were freeze-dried to enhance mechanical properties, increase the porosity of the dressing, and facilitate further evaluations. A variety of analytical methods, including scanning electron microscopy (SEM), X-ray dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FT-IR) were employed to characterize the composites. The developed composites exhibited high porosity and a swelling degree exceeding 200% after 3 days. Additionally, water absorption capacity increased with higher alginate concentrations in the samples. Furthermore, they demonstrated significant antibiofilm activity against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, with the samples containing 4% alginate showing the best results.
Infected skin wound healing involves a series of dynamic and complex physiological processes. In this study, we reported a dissolvable microneedle (MN) with pullulan as the matrix material. The antimicrobial … Infected skin wound healing involves a series of dynamic and complex physiological processes. In this study, we reported a dissolvable microneedle (MN) with pullulan as the matrix material. The antimicrobial peptide LL37 was immobilized in situ within ZIF-8 to form hybrid nanoparticle LL37@ZIF-8 (LZ). This nanoparticle was then loaded onto the tip of the microneedle along with Prussian Blue (PB) nanozymes to obtain PB+LZ@MN, which exhibits both antimicrobial and antioxidative activities, for the healing of infected skin wounds. The MN, with good mechanical properties, could rapidly dissolve its tip upon insertion into the skin, releasing LZ and PB into the wound within 3 min. The MN had good physicochemical properties and biocompatibility and was shown to reduce inflammation and stimulate angiogenesis by enhancing collagen deposition and re-epithelialization in the Sprague-Dawley (SD) rat skin defect infection model. On the 10th day of wound healing, the healing rate of the PB+LZ@MN group was as high as 99%, which was significantly higher than that of the control at 84%, significantly accelerating the healing of the infected wound. This multifunctional MN is expected to provide a competitive biomaterial for accelerated infected wound healing.
The topical administration of drugs on the skin by nanovesicular systems can represent a tool to treat skin pathologies. The study of nanovesicle biodistribution after skin administration is crucial to … The topical administration of drugs on the skin by nanovesicular systems can represent a tool to treat skin pathologies. The study of nanovesicle biodistribution after skin administration is crucial to understanding their transdermal potential. A formative study enabled us to investigate the influence of some methods in the production of nanovesicles based on phosphatidylcholine, differing in their ethanol amount. Particularly, both liposomes and ethosomes produced by different methods, i.e., microfluidics and solvent injection, were considered. The evaluation of size distribution, shape and internal morphology was performed using photon correlation spectroscopy, cryogenic electron microscopy, hyperspectral dark-field microscopy and small-angle X-ray scattering. Transmission electron microscopy was then used to observe and compare the transdermal passage of selected liposomes and ethosomes applied to human skin explants in a bioreactor. The mean diameters of nanovesicles prepared by the ethanol injection method were smaller with respect to those obtained by microfluidics, measuring roughly 140 and 230 nm, respectively. The uni- or multilamellar ultrastructure of the vesicles was influenced by the solvent injection procedure. Ultrastructural analysis of skin penetration revealed (i) the ability of intact vesicles to cross the different skin layers, with ethosomes produced by the water injection method showing greater transdermal potential and (ii) the role of ethanol as a penetration enhancer.
Introduction: solid lipid nanoparticles (SLNs) have emerged as promising drug delivery systems, standing out for their biocompatibility and stability.Objective: to evaluate the biocompatibility of SLNs formulated with myristyl myristate (MM) … Introduction: solid lipid nanoparticles (SLNs) have emerged as promising drug delivery systems, standing out for their biocompatibility and stability.Objective: to evaluate the biocompatibility of SLNs formulated with myristyl myristate (MM) in human lymphocytes through cytotoxicity, genotoxicity, and oxidative stress assays.Methods: SLNs were synthesized using sonication and characterized in terms of size, polydispersity index, and zeta potential. Concentrations ranging from 18.75 to 300.00 μg/ml were selected for in vitro assays. Cell viability was assessed using the MTT assay, while genotoxicity was analyzed through the Comet assay. Lipid peroxidation was measured by quantifying thiobarbituric acid reactive substances (TBARs).Results: after 24 hours of exposure, cell viability remained above 90% at all concentrations. However, after 48 hours, viability decreased at concentrations of 150 and 300 μg/ml. No significant DNA damage or changes in lipid peroxidation levels were observed under any tested condition.Conclusion: these findings suggest that MM-based SLNs exhibit high in vitro biocompatibility, with no relevant short-term cytotoxic or genotoxic effects. However, further studies in in vivo models and under prolonged exposure conditions are necessary to assess their safety for biomedical applications.
Transdermal drug delivery systems (TDDS) present a non-invasive and patient-compliant alternative to conventional routes of administration by facilitating drug transport across the skin barrier. Upon topical application to intact skin, … Transdermal drug delivery systems (TDDS) present a non-invasive and patient-compliant alternative to conventional routes of administration by facilitating drug transport across the skin barrier. Upon topical application to intact skin, the drug permeates the stratum corneum, diffuses through the underlying epidermal and dermal layers, and subsequently reaches systemic circulation via capillary networks. This approach enables controlled and sustained drug release, enhances bioavailability, and circumvents the limitations associated with oral and parenteral delivery, including first-pass metabolism and injection-associated discomfort. The human skin, comprising the epidermis, dermis, and hypodermis, poses a formidable barrier, particularly at the stratum corneum, necessitating the use of advanced penetration enhancement techniques. Among these, microneedle-based technologies have emerged as a promising strategy, offering transient and minimally invasive disruption of the skin barrier. Fabricated from biocompatible materials such as silicon, metals, polymers, ceramics, or sugars, microneedles exist in various designs-including solid, coated, dissolvable, and hydrogel-forming types-each tailored for specific drug release profiles. These systems hold potential not only for therapeutic drug delivery but also for diagnostics and cosmetic applications. Regulatory oversight by agencies like the FDA classifies microneedle-based systems as combination products, requiring comprehensive evaluation including sterility, stability, safety, and performance testing. The development of harmonized regulatory frameworks could further facilitate their clinical translation and market integration. Keywords: Transdermal drug delivery systems (TDDS), Microelectronics and microelectromechanical systems (MEMS), White adipose tissue (WAT), Microneedle technology, Polymers
Objective: To identify the importance of Solid lipid nanoparticles (SLNs), their most recent methods of preparation and the drugs, lipid(s) and surfactant(s) most recently used for carrier development. Methods: Original … Objective: To identify the importance of Solid lipid nanoparticles (SLNs), their most recent methods of preparation and the drugs, lipid(s) and surfactant(s) most recently used for carrier development. Methods: Original articles were identified through searches of MEDLINE/PubMed for within the last 5 years (2020-February 2025), with the following search terms; solid lipid nanoparticles. The main aim was to find original articles/ research, this led to another search but excluded evaluation. Study Selection and exclusion criteria: Articles that discussed active pharmaceutical ā€œdrugsā€ were selected for this study and exclusion criteria of ā€œNOT review NOT MRNA NOT DNA NOT RNAā€ to narrow down the articles. Data Synthesis: More than 500 articles were identified and further reviewed in the literature and were categorized according to the method in which the SLN were prepared; homogenization and/or high-pressure homogenization, ultrasonication, solvent injection and/or solvent evaporation phase inversion, microemulsion/emulsification, nano spray drying and/or others and combination methods. Conclusion: As more specific drug targeting and drug delivery systems become more of an interest in the drug development field, solid lipid nanoparticles will be of continuance importance for a strategic role in nanoparticle formulations. Keywords: Solid lipid nanoparticles (SLNs), Homogenization, Ultrasonication, Solvent injection
Objectives: To introduce a novel method for apical lesion sampling using a protected paper point device and to evaluate its effectiveness and robustness during the sampling process in vitro. Methods: … Objectives: To introduce a novel method for apical lesion sampling using a protected paper point device and to evaluate its effectiveness and robustness during the sampling process in vitro. Methods: A prototype for apical sample collection was developed as an adaptation of the Micro-Apical Placement System-the device features a highly tapered screw head with a thin, hollow, stainless-steel tube and an internal wire piston. Standardized 5 mm paper points (ISO 10; PD Dental, Switzerland) served as carrier material. The prototype was tested using 30 Ɨ 3D-printed, single-rooted tooth models inoculated using two bacterial strains (Staphylococcus epidermidis and Escherichia coli) to simulate apical and intraradicular bacterial infections, respectively. The sampling process involved collecting and analyzing samples at specific timepoints, focusing on the presence or absence of E. coli contamination. Following sample collection, cultural detection of bacterial presence was performed by incubating the samples on agar plates to confirm the presence of E. coli. Samples were collected as follows: S0 (sterility control of the prototype), P0 (sterility control of the tooth model), P1 (apical sample collected with the CAPS (controlled apical sampling) device, and P2 (contamination control sample to check for the presence of E. coli inside the root canal). Results: Handling of the CAPS prototype was straightforward and reproducible. No loss of paper points or complications were observed during sample collection. All sterility samples (P0, S0) were negative for tested microorganisms, confirming the sterility of the setup. P2 samples confirmed the presence of E. coli in the root canal in all trials. The P1 samples were free from contamination in 86.67% of trials. Conclusions: The CAPS method for apical sampling demonstrated advances in the successful and precise sample collection of apically located S. epidermidis and will be a useful tool for endodontic microbiological analysis. Its user-friendly design and consistent performance highlight its potential for clinical application, contributing to more accurate microbial diagnostics and later patient-specific therapeutic approaches in endodontic treatments.
Study’s Excerpt:• Recent developments in nanoemulsion systems for both superficial and deep-skin applications was reviewed.• It uniquely synthesizes clinical translation barriers, regulatory gaps, and emerging trends like nanoemulgels.• Multiple complementary … Study’s Excerpt:• Recent developments in nanoemulsion systems for both superficial and deep-skin applications was reviewed.• It uniquely synthesizes clinical translation barriers, regulatory gaps, and emerging trends like nanoemulgels.• Multiple complementary approaches across primary databases were employed.• Nanoemulsions enhance drug permeability with improvements ranges to over 39-fold compared to conventional creams.• Further clinical studies remain necessary to confirm long-term safety.Full Abstract:Objective: This review explores recent developments in nanoemulsion systems for both superficial and deep-skin applications, uniquely synthesizing clinical translation barriers, regulatory gaps, and emerging trends like nanoemulgels.Methods: A comprehensive narrative review was conducted using multiple complementary approaches across primary databases (PubMed, ScienceDirect) and secondary sources (Google Scholar). Enhanced search capabilities through Elicit and Research Rabbit were utilized to map relevant literature connections. Primary search terms included "nanoemulsion drug delivery," "dermatological applications," "skin penetration enhancement," and "topical nanoemulsions." The review focused on literature from 2019-2024 with strategic inclusion of foundational papers, encompassing original research, clinical studies, and review articles.Results: Nanoemulsions enhance drug permeability with improvements ranging from several-fold to over 39-fold compared to conventional creams through fluidizing or altering the stratum corneum's lipid matrix, improving solubility, stability, and bioavailability. Critical characteristics such as droplet size and zeta potential determine stability and skin absorptivity, enabling targeted delivery of anti-inflammatory agents and active ingredients while reducing systemic side effects compared to conventional treatments. Despite showing a favourable safety and non-irritant profile, the analysis revealed significant clinical translation barriers and regulatory gaps that limit widespread adoption.Conclusion: Further clinical studies remain necessary to confirm long-term safety. Future integration with wearables and smart delivery systems may revolutionize dermatological treatment paradigms, positioning nanoemulsions as a transformative technology in topical therapeutics.
ABSTRACT Skin aging prevention is increasingly important in cosmetics. Topical application of antioxidants protects the skin against reactive oxygen species (ROS) generated as a result of continuous exposure to UV … ABSTRACT Skin aging prevention is increasingly important in cosmetics. Topical application of antioxidants protects the skin against reactive oxygen species (ROS) generated as a result of continuous exposure to UV radiation. Herbal oils offer significant anti‐aging potential due to their antioxidant content. Lipid nanoparticles (i.e., SLN and NLC) have been comprehensively evaluated for dermal drug delivery and cosmetic applications since they offer enhanced skin hydration and improved percutaneous penetration. The latest approach for dermal application is the usage of semi‐solid lipid nanoparticle dispersions, which offer unique advantages. Semi‐solid SLN/NLC dispersions have a suitable consistency for dermal application and can be prepared by a one‐step production method without additional excipients. Furthermore, they preserve the colloidal particle size in spite of their semi‐solid consistency. Development of novel cosmeceutical semi‐solid NLC dispersions containing valuable herbal oils such as pomegranate seed, argan, grape seed, and coconut oils was aimed at in this study. Formulation optimization was performed using a modeling program based on response surface methodology (RSM). Optimum semi‐solid NLC formulation (Opt‐NLC) was prepared using Compritol 888ATO and argan oil at amounts of 0.8403 and 0.5457 g, respectively. The particle size of the Opt‐NLC formulation was found to be 188.6 ± 3.58 nm, which falls within the targeted size range. PDI was also reduced and a more uniform particle size was obtained by optimization. Rheological and mechanical characterization results revealed that Opt‐NLC has suitable properties in terms of product performance and consumer compliance. As a result, formulation optimization of semi‐solid NLC dispersions containing antioxidant herbal oils was successfully performed using RSM methodology.
Introduction and Objective: Patients with type 1 and type 2 diabetes are subjected to insulin injection therapies. Repeated subcutaneous insulin administrations leads to physiological and psychological issues, such as low … Introduction and Objective: Patients with type 1 and type 2 diabetes are subjected to insulin injection therapies. Repeated subcutaneous insulin administrations leads to physiological and psychological issues, such as low adherence, infections, subcutaneous nodules, scarring, and so on. Insulin microneedles enables minimally invasive delivery of insulin, reducing adverse effects of insulin therapy in patients. Herein, we designed a porous insulin microneedle that can release insulin in a controlled manner for diabetes treatment. Methods: Porous microneedles were constructed by gelatin methacrylamide loaded with insulin. We characterized the porous insulin microneedles via optical microscopy and scanning electron microscopy. Biocompatibility was evaluated by utilizing CCK8 assays. To observe penetration effects, agarose hydrogel was used for simulating human skin. The release of insulin from the microneedles was investigated by labeling insulin with FITC. Diabetic mouse models were established and treated with porous insulin microneedles, followed by continuous observation of blood glucose levels. Results: The porous microneedles were demonstrated homogeneous microneedle arrays under microscopy. Transversal section of the microneedles had porous structure, capable of loading macromolecules including insulin. It was shown good biocompatibility when culturing with cells. As minimally invasive patches, the fabricated porous insulin microneedles can penetrate through the skin model, which released insulin into the subcutaneous spaces rapidly. Diabetic mouse models were successfully established with high blood glucose levels. Treated with the porous insulin microneedles, the hyperglycemia was ameliorated in diabetic mice. Conclusion: The resultant porous insulin microneedles can delivery insulin efficiently in a minimally invasive manner, reducing high blood glucose levels of diabetic mice. It is innovative for diabetes treatment, drug delivery, and smart medicine. Disclosure J. Li: None. Z. Huan: None. L. Li: None. Funding National Natural Science Foundation Major International (Regional) Joint Research Program (82320108003); National Natural Science Foundation (82170845, 82000740, 81970717); Key Research &amp; Developement Program (No.BE2022853); Medical Key Discipline (ZDXK202203) of Jiangsu Province; SEU Innovation Capability Enhancement Plan for Doctoral Students (CXJH_SEU 24223)
Alzheimer's disease (AD) is a complex neurodegenerative that affects over 55 million people worldwide, a number expected to double by 2050 due to aging populations. This growing prevalence imposes immense … Alzheimer's disease (AD) is a complex neurodegenerative that affects over 55 million people worldwide, a number expected to double by 2050 due to aging populations. This growing prevalence imposes immense societal and economic burdens on healthcare systems and caregivers. AD is challenging to treat with monotherapy, making combination therapy a more effective approach. This study focuses on delivering Rivastigmine tartrate (RIV), and Nilotinib hydrochloride monohydrate (NIL), to the brain to achieve synergistic effects against AD. The optimal ratio of the drug combination was determined using the combination index that was performed using the Neuro2a cells line. It was found to be 1:1, emphasizing the synergistic effect against the cell lines. So, nanostructured lipid carriers (NLCs) were loaded with RIV and NIL, both individually and in combination, developed and optimized in this study. The developed formulations were thoroughly characterized for globule size, polydispersity index (PDI), and entrapment efficiency (EE) for each drug and the combination. The globule size was > 200 nm, PDI > 0.3; EE < 85% in all the developed formulations. On performing an in vitro cell availability study it was found that developed NLCs showed a 1.3 to 1.4-fold increase in the viability of the cells. On conducting an in vivo study, the concentration in the brain following administration of different formulations was in the order of RIV-NIL-NLC > NIL-NLC > RIV-NLC > RIV-NIL SUS > NIL-SUS > RIV-SUS. There was a 3.5 to 5-fold increase in the concentration of RIV and NIL in the brain when administered as RIV-NIL-NLC. So, it can be concluded that the NLCs with combined drugs showed promising results, enhancing drug permeability through the intranasal route, therefore could be used for treating AD.
Conventional blood-based detection methods for biomarkers and analytes face significant limitations, including complex processing, variability in blood components, and the inability to provide continuous monitoring. These challenges hinder the early … Conventional blood-based detection methods for biomarkers and analytes face significant limitations, including complex processing, variability in blood components, and the inability to provide continuous monitoring. These challenges hinder the early diagnosis and effective management of various health conditions. Electrochemical microneedles (MNs) have emerged as a minimally invasive and highly efficient platform to overcome these barriers, enabling continuous molecular monitoring by directly accessing the interstitial fluid. Electrochemical MNs offer several advantages, including reduced patient discomfort, real-time data acquisition, enhanced specificity, and potential applications in wearable, long-term monitoring. In this review, we first analyze material selection and fabrication techniques to optimize sensor performance, stability, and biocompatibility. We then examine diverse detection strategies utilized in electrochemical MNs, including enzyme-based, aptamer-based, and antibody-based sensing mechanisms, each offering unique benefits in sensitivity and selectivity. Finally, we highlight the integration of electrochemical MN technology with multi-target detection, AI-driven analytics, and theragnostic capabilities. This convergence offers strong potential for smart healthcare and precision medicine. Through these technological innovations, electrochemical MNs are expected to play an important role in advancing continuous, noninvasive health monitoring and personalized medical care.