Search Results (59)

Drug delivery systems have long faced a fundamental challenge: achieving high drug-loading efficiency, precise control over release, and in vivo safety simultaneously is a difficult task. Cellulose and its derivatives are abundant and renewable, exhibiting good biocompatibility, which makes them promising candidates for drug delivery materials. Representative derivatives, such as carboxymethyl cellulose, hydroxypropyl methyl cellulose, and ethyl cellulose, as well as nanocellulose, including cellulose nanocrystals, cellulose nanofibrils, and bacterial nanocellulose, have enabled the development of diverse carrier formats, including hydrogels, aerogels, films, and particulate systems. Recent advances include pH-responsive bacterial nanocellulose/carboxymethyl cellulose hydrogels for oral ibuprofen delivery, carboxylated nanocellulose/polyethylene glycol/β-cyclodextrin composite aerogels for gastric-selective release of imatinib, and hydroxypropyl methyl cellulose-based microneedle patches for transdermal co-delivery of sumatriptan succinate and naproxen sodium. These examples highlight how cellulose-based systems can be engineered for site-selective delivery, sustained release, and multi-stimuli responsiveness. In this review, we summarize the structural features of cellulose derivatives and nanocellulose, discuss the design principles and release mechanisms of representative delivery platforms, and outline current challenges in manufacturability, safety evaluation, and clinical translation. Full article

Background/Objectives: Skin aging and wrinkle formation are primarily driven by ultraviolet (UV)-induced oxidative stress and inflammation. Resveratrol (RSV) and nicotinamide (NCT) possess potent anti-aging properties but suffer from poor skin penetration. This study aimed to develop an advanced transdermal delivery system incorporating RSV/NCT-loaded cerosomes within poly(lactic-co-glycolic acid) (PLGA) microneedles to enhance skin permeation and anti-aging performance. Methods: RSV/NCT-loaded cerosomes were formulated using thin-film hydration of phosphatidylcholine, ceramides (III, IIIB, and VI), and poloxamer surfactants, subsequently optimized via a D-optimal mixture design. PLGA microneedles with optimized cerosomes were tested for their mechanical strength, penetration, drug loading, and release. Ex vivo permeation and in vivo evaluations were performed using a UVA-induced skin wrinkling model. Results: Optimized cerosomes exhibited high entrapment efficiency for RSV and NCT (91 ± 0.56% and 85 ± 0.56%, respectively), nanoscale size (195 ± 0.78 nm), low polydispersity (0.23 ± 0.01), and a negative zeta potential (−22 ± 0.45 mV). PLGA microneedles exhibited sufficient mechanical integrity and effective penetrability through Parafilm^® layers. Microneedle-loaded cerosomes enabled sustained drug release (approximately 65–70% over 48 h) and enhanced ex vivo permeation, approximately for NCT and RSV (1450 μg/cm² and 1000 μg/cm², respectively). In vivo investigations revealed improved skin appearance, restoration of epidermal thickness and collagen architecture, reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, NLRP3), reduced oxidative stress biomarkers (GSH, GPx, MDA, SOD), and genetic upregulation of VEGF, TGF-β1, and β-Catenin. Conclusions: The RSV/NCT cerosome-encapsulated PLGA microneedle system offers a promising, minimally invasive approach with superior transdermal delivery, sustained efficacy, and significant anti-aging benefits. Full article

Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 °C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV–Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 ± 45 µm length; 330 µm base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 ± 0.03 N/needle and achieved insertion depths of approximately 396 µm in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems. Full article

Background/Objectives: Capric acid (CA)–therapeutic deep eutectic systems (THEDES) are emerging as a distinct class of biofunctional matrices capable of reshaping drug solubilization, permeability, and bioactivity. Methods: Relevant studies on CA–THEDES were identified through targeted database searches and screened for evidence on their design, mechanisms, and pharmaceutical performance. Results: This review synthesizes current evidence on their structural design, mechanistic behavior, and pharmaceutical performance, revealing several unifying principles. Across multiple drug classes, CA consistently drives strong, directional hydrogen bonding and drug amorphization, resulting in marked solubility enhancement and stabilization of non-crystalline or supersaturated states relative to crystalline drugs or conventional solvent systems. Its amphiphilic C10 chain further contributes to membrane fluidization, which explains the improved transdermal and transmucosal permeation repeatedly observed in CA-THEDES. Additionally, synergistic antimicrobial and anticancer effects reported in several systems confirm that CA acts not only as a solvent component but as a bioactive co-therapeutic. Collectively, the reviewed data show that CA serves as a structurally determinant element whose dual hydrogen-bonding and membrane-interacting roles underpin the high pharmaceutical performance of these systems. However, gaps remain in long-term stability, toxicological profiling, and regulatory classification. Emerging Artificial Intelligence (AI) and Machine Learning (ML)-guided predictive approaches offer promising solutions by enabling rational selection of eutectic partners, optimal ratios, and property optimization through computational screening. Conclusions: Overall, CA-THEDES represent a rationally designable platform for next-generation drug delivery, where solvent functionality and therapeutic activity converge within a single, green formulation system. Full article

Achieving optimal skin penetration with bioactive cosmetic ingredients, such as epidermal growth factor (EGF), presents ongoing challenges. This study introduces a novel elastosome-based EGF delivery system co-loading dexpanthenol, which achieves superior skin penetration and multifunctional cosmetic efficacy compared with a conventional liposome formulation. The EGF FLEXIR-SOME formulation was characterized to determine its physicochemical properties measured for comparison against a conventional liposome control. Efficacy and safety were confirmed through in vitro and in vivo evaluations, including clinical trials of the formulation and primary skin irritation tests. The formulated EGF FLEXIR-SOME particles exhibited an average diameter of 124.8 nm and a zeta potential of −57.53 mV, demonstrating enhanced stability and skin penetration relative to the control. The results of clinical trials confirmed significant efficacy in anti-aging, moisture, skin barrier improvement, and hyperpigmentation reduction. Additionally, primary skin irritation tests classified the product as a non-irritant. In conclusion, an elastosome-based EGF formulation significantly enhances skin penetration and bioavailability. The formulation effectively improves skin elasticity, hydration, and barrier function while simultaneously reducing visible signs of aging and pigmentation. This study successfully developed an innovative formulation utilizing elastosome technology, maximizing the transdermal efficiency and stability of EGF, thereby offering a novel strategy for functional cosmeceutical development. Full article

This review systematically outlines recent advances in long-acting microneedle-based transdermal drug delivery systems. It begins by introducing the fundamental principles of microneedles (MNs) as a minimally invasive technology and categorizes them by delivery mechanism into solid, coated, dissolving, hollow, hydrogel-forming, and biodegradable types. The review then discusses the design strategies and material platforms engineered for sustained drug release. A key focus is on biodegradable synthetic polymers, such as polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL), and natural polymers like silk fibroin (SF) and chitosan (CS), which enable prolonged drug release through their tunable degradation rates. Furthermore, it describes the incorporation of advanced drug carriers, including liposomes and polymeric nanoparticles/microparticles, into MNs to further extend release duration and enhance drug-loading capacity. Finally, the major challenges for clinical translation are addressed, including ensuring batch-to-batch consistency in manufacturing, maintaining sterility, and the necessity for more comprehensive validation of long-term in vivo efficacy and safety. Full article

In recent years, microneedles (MNs) have emerged as a novel transdermal drug delivery technology, offering advantages such as avoidance of the first-pass effect, pain-free and minimally invasive administration, and convenient application. However, conventional MNs still face challenges, including slow detachment of MN tips from the base substrate and limited transdermal efficiency. This review systematically summarizes recent advances in MNs-mediated gas delivery for rapid separation, enhanced drug penetration, and combined therapy. The discussion encompasses the benefits and limitations of MNs and recent developments in MN-facilitated gas delivery to accelerate separation rate and improve delivery efficiency. By analyzing the therapeutic roles of various gases (e.g., H₂, O₂, NO, H₂S, CO, CO₂) and their synergistic potential when combined with MNs, this review also provides insights and references for the further application of gas-assisted MN systems for combined therapy in various disease treatments. Full article

This study reports the development and optimization of a Melissa officinalis oil-based nanoemulgel for transdermal delivery using a Design-of-Experiments (DoE) approach. A Central Composite Design (CCD) was applied to optimize Tween 80 concentration and homogenization time, resulting in a nanoemulsion with a droplet size of 127.31 nm, PDI of 17.7%, and zeta potential of −25.0 mV, indicating good colloidal stability. FTIR analysis confirmed the presence of functional groups such as O–H, C=O, and C–O–C, supporting the oil’s phytochemical richness and therapeutic potential. DSC analysis revealed enhanced thermal stability and successful encapsulation, while SEM imaging showed a uniform and spherical microstructure. The drug release followed Higuchi kinetics (R² = 0.900), indicating diffusion-driven release, with the Korsmeyer–Peppas model (n = 0.88) suggesting anomalous transport. Antibacterial studies showed inhibition of Staphylococcus aureus (MIC = 250 µg/mL) and Escherichia coli (MIC = 500 µg/mL). In vivo anti-inflammatory testing demonstrated significant edema reduction (p < 0.05) using a carrageenan-induced rat paw model. These results support the potential of Melissa nanoemulgel as a stable and effective topical therapeutic for inflammatory and microbial skin disorders. Full article

Wound healing remains a significant clinical challenge worldwide, and effective management strategies are essential for improving outcomes. This study investigates the therapeutic potential of the AcuCool™ system, a novel multifunctional device that combines high-velocity CO₂ cryotherapy with intradermal delivery of epidermal growth factor (EGF), in promoting wound healing. Using a full-thickness skin wound model in Sprague Dawley rats, we compared the effects of Device+EGF treatment to those of conventional microneedling-based EGF delivery and untreated controls. Macroscopic assessments revealed significantly accelerated wound closure in the Device+EGF group. Histological analysis showed enhanced re-epithelialization, reduced inflammatory cell infiltration, and increased collagen deposition. Molecular evaluations further demonstrated downregulation of pro-inflammatory markers (TNF-α, IL-1β, MCP-1) and upregulation of remodeling-related genes including TGF-β1, Collagen I, and Vimentin. In addition, nitrite assays confirmed reduced local nitric oxide levels, indicating suppression of oxidative stress. The AcuCool™ platform offers precise, non-invasive drug delivery with dual physical and biochemical therapeutic mechanisms, enabling superior control of inflammation and tissue regeneration. These findings suggest that AcuCool™ represents a promising therapeutic strategy for accelerating wound healing in acute models. While further studies are warranted in chronic wound settings, this approach may hold translational potential for future clinical applications. Full article

A transdermal drug delivery system based on hydrogel patches was explored, leveraging their sustained release properties and biocompatibility. Despite these advantages, conventional hydrogels often lack proper adhesion to the skin, limiting their practical application. To address this issue, we designed a skin-adhesive hydrogel using a polyacrylamide (PAM)/polydopamine (PDA) dual-network structure. The matrix combines the mechanical toughness of PAM with the strong adhesive properties of PDA, derived from mussel foot proteins, enabling firm tissue attachment and robust performance under physiological conditions. To demonstrate its applicability, the hydrogel was integrated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the hydrophobic antioxidant vitamin E as a model compound. The resulting PAM/PDA@VitE hydrogel system exhibited improved swelling behavior, high water retention, and prolonged release of α-tocopherol. These results suggest that the PAM/PDA hydrogel platform is a versatile vehicle not only for vitamin E, but also for the transdermal delivery of various cosmetic and therapeutic agents. Full article

Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation. Full article

Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article

Background: Liposome particles with smaller sizes could increase transdermal drug delivery efficacy for enhanced skin penetration. While microfluidic methods have enabled controlled liposome synthesis, achieving efficient production of ultrasmall nanoliposomes (NLP_US) with a size smaller than 40 nm yet remains an unmet challenge. Methods: In this study, we employed a helical-blade-strengthened co-flow focusing (HBSCF) device to efficiently synthesize NLP_US, which demonstrated superior skin permeation and retention. Results: Liposome formulation primarily contains unsaturated lecithin, which endows an unprecedented capacity to NLP_US to scavenge reactive oxygen species (ROS). Moreover, NLP_US can effectively encapsulate a broad spectrum of anti-aging agents, including coenzyme Q10 (CoQ10), while preserving its physical properties. In a photoaged skin model, topical application of CoQ10-loaded NLP_US (CoQ10@NLP_US) inhibited ultraviolet B (UVB)-induced matrix metalloproteinase-1 (MMP-1) production, and promoted collagen type I (Col-I) synthesis in skin cells, thereby effectively rejuvenating the photoaged skin. Conclusions: This study presents a straightforward and efficient method for the production of NLP_US, thereby offering a promising platform for transdermal delivery of diverse therapeutic agents. Full article

Background/Objectives: Cyclovirobuxine D, a natural compound derived from the medicinal plant Buxus sinica, demonstrates a diverse array of therapeutic benefits, encompassing anti-arrhythmic properties, blood pressure regulation, neuronal protection, and anti-ischemic activity. However, its limited solubility hinders the bioavailability of current oral and injectable formulations, causing considerable adverse reactions and toxicity. Methods: In this investigation, we embarked on an unprecedented exploration of the skin penetration potential of cyclovirobuxine D utilizing chemical penetration enhancers and niosomes as innovative strategies to enhance its dermal absorption. These strategies were rigorously tested and optimized. Results: Among the tested chemical penetration enhancers, azone emerged as the most potent, achieving a 4.55-fold increase in skin penetration compared to the untreated group. Additionally, when encapsulated within niosomes, primarily composed of Span60 and cholesterol, the skin penetration of cyclovirobuxine D was notably enhanced by 1.50-fold. Furthermore, when both cyclovirobuxine D and azone were co-encapsulated within the niosomes, the skin penetration of cyclovirobuxine D was remarkably elevated by 8.10-fold compared to the solvent-dispersed group. This enhancement was corroborated through rigorous in vitro and in vivo experiments. Notably, the combination of other chemical penetration enhancers with niosome encapsulation also exhibited synergistic effects in enhancing the skin penetration of cyclovirobuxine D. Conclusions: These findings provide a compelling rationale for the administration of cyclovirobuxine D via skin-mediated transdermal delivery, offering superior safety, efficacy, and convenience. The innovative combination of niosomes and chemical penetration enhancers represents a novel system for the transdermal delivery of cyclovirobuxine D, holding immense promise for clinical applications in the treatment of brain, neuronal, and cardiovascular disorders. Full article

Skin diseases are a common health problem affecting millions of people worldwide. Effective treatment often depends on the precise delivery of drugs to the affected areas. One promising approach is currently the transdermal drug delivery system (TDDS), whose significant challenge is the poor penetration of many compounds into the skin due to the stratum corneum (SC), which acts as a formidable barrier. To overcome this limitation, nanocarriers have emerged as a highly effective alternative. This review discusses the use of liposomes and ethosomes for transdermal drug delivery. Liposomes are micro- or nanostructures consisting of a lipid bilayer surrounding an aqueous core. They facilitate transdermal drug penetration and may be advantageous for site-specific targeting. Some methods of treating skin diseases involve incorporating drugs such as acyclovir, dithranol, and tretinoin or bioactive compounds such as fluconazole, melanin, glycolic acid, kojic acid, and CoQ10 into nanocarriers. The inability of liposomes to pass through the narrowed intercellular channels of the stratum corneum led to the invention of lipid-based vesicular systems such as ethosomes. They are structurally similar to conventional liposomes, as they are prepared from phospholipids, but they contain a high ethanol concentration. Ethosomes are noninvasive carriers that allow drugs to reach the deep layers of the skin. Examples of commonly used substances and drugs combined with ethosomes in cosmetics include methotrexate, ascorbic acid, vitamin A and E, and colchicine. A significant development in this area is the use of rutin-loaded ethosomes. Encapsulating rutin in ethosomes significantly improves its stability and enhances skin penetration, allowing more efficient delivery to deeper skin layers. In cosmetics, rutin–ethosome formulations are used to protect the skin from oxidative stress, reduce redness, and improve capillary strength, making it a valuable formulation in anti-aging and anti-inflammatory products. The results of the first clinical trial of the acyclovir–ethosome formulation confirm that ethosomes require further investigation. The work provides an update on recent advances in pharmaceutical and cosmetic applications, mentioning the essential points of commercially available formulations, clinical trials, and patents in the recent past. Full article