Search Results (368)

The Transdermal Drug Delivery System (TDDS) offers several benefits, such as enhanced patient adherence, controlled release, reduced gastric irritation, and the bypassing of the first-pass metabolism. However, not all drugs can be delivered through this route in effective doses. Biodegradable microneedles (BMn) are designed to improve TDDS. This review outlines various types of BMn and their fabrication methods. BMn are produced in different forms, including hollow, solid, dissolve, and hydrogel-forming versions, which have garnered significant attention. These innovative BMn do not contain drugs themselves but instead absorb interstitial fluid to create continuous channels between the dermal microcirculation and a drug-containing patch. Several types of BMn have been tested and approved by regulatory bodies. The use of BMn technology is rapidly growing in point-of-care applications, attracting significant interest from both researchers and healthcare providers. BMn-based Point-of-care (POC) devices have high efficacy for finding various analytes of clinical interests and transdermal drug administration in a minimally invasive manner owing to BMn’ micro-size sharp tips and ease of use. Porous BMn technology may have a very rising future in the case of a vaccine delivery system. Full article

Treating bacterial infections has become increasingly difficult due to the rise in antibiotic-resistant bacterial strains. Strategies involving the targeted delivery of antibiotics have been proposed to minimize the administered antibiotic doses. This study aims to develop the first double-modified nanovehicle capable of increasing bacterial membranes’ permeability while specifically targeting Staphylococcus aureus, one of the foremost pathogens responsible for global mortality rates. Thus, polymeric NPs composed of poly(lactic-co-glycolic acid) (PLGA) were produced, and their surface was modified with TAT peptide to increase the membranes’ permeability and folic acid (FA) to direct the NPs to S. aureus. The nanosystem showed spherical morphology with sizes of 174 ± 4 nm, a monodisperse population (polydispersity index of 0.08 ± 0.02), and a zeta potential of −2.5 ± 0.1 mV. The NPs remained stable for up to four months during storage. Fluorescence-based flow cytometry analysis proved that the double modification of PLGA NPs increased the interaction of the NPs with S. aureus, with fluorescence increasing from 71 ± 3% to 87 ± 1%. The nanosystem slightly affected the growth curve of S. aureus by extending both the lag time (from 2.5 ± 0.2 to 2.88 ± 0.4 h) and the exponential phase, as evidenced by an increase in the half-maximum growth time (from 3.9 ± 0.2 to 4.4 ± 0.1 h). Furthermore, the nanocarrier showed no toxicity for human dermal fibroblast cells, maintaining a 100% cell viability at the highest concentration tested (100 µM). Therefore, the proposed FA/TAT-functionalized nanocarrier presented promising features to be successfully used as a delivery vehicle of antimicrobials to fight S. aureus. Full article

Background/Objectives: Ultradeformable liposomes represent an established platform for topical delivery of antioxidant compounds, thanks to their structural flexibility and ability to enhance skin permeation, but standardized manufacturing protocols are still lacking. This study presents a microfluidic-based strategy for the scalable production of ultradeformable liposomes encapsulating Stellaria media extract, a polyphenol-rich phytocomplex with strong antioxidant activity. Methods: Liposomes were produced with a GMP-like microfluidic platform enabling fine control of formulation parameters and high reproducibility under conditions directly transferable to continuous manufacturing. Process optimization tested different total flow rates. Characterization included particle size and distribution, encapsulation efficiency, colloidal stability and kinetics of release. Permeation was assessed with Franz diffusion cells using human stratum corneum and epidermidis membranes. Results: Optimal conditions were a flow rate ratio of 3:1 and a total flow rate of 7 mL/min, yielding ultradeformable liposomes with a mean size of 89 ± 1 nm, a polydispersity index < 0.25, and high encapsulation efficiency (72%). The resulting formulation showed long-term colloidal stability and controlled release. Diffusion studies demonstrated a 2-fold increase in permeation rate compared to the free extract. Conclusions: These findings highlight the potential of microfluidics as a robust and scalable technology for the industrial production of ultradeformable liposomes designed to enhance the dermal delivery of bioactive phytocomplex for both pharmaceutical and cosmeceutical applications. Full article

The treatment of parasitic infections has evolved in terms of effectiveness and the prevention of drug resistance. This is highlighted by the discovery of ivermectin (IVM), a macrocyclic lactone and broad-spectrum antiparasitic agent. IVM garnered scientific attention by presenting a therapeutic alternative in the field of veterinary medicine due to its control of multiple parasite species, including nematodes and soil-transmitted helminths. Shortly after its discovery, IVM was approved for human use by the World Health Organization (WHO) and United States Food and Drug Administration (FDA) for combating head lice, onchocerciasis, rosacea, scabies, and worm infestations within the gastrointestinal tract (GIT). In veterinary medicine, IVM is available in a range of formulations and can be administered via different routes (i.e., oral, topical, and parenteral), whereas for humans, IVM is only approved as a single oral dose and dermal cream. Establishing a comprehensive overview of IVM’s applications in both human and veterinary medicine is necessary, particularly in light of its repurposing potential as a treatment for various conditions and emerging diseases. Given its primary application in veterinary medicine, there is a need to enhance the development of dosage forms suitable for human use. Therefore, this review details the discovery, mechanisms, and applications of IVM, while also examining the challenges of resistance, side-effects, and controversy surrounding its use, to ultimately emphasize the importance of targeted, optimized IVM delivery via tailored dosage form development in animals and humans as part of the One Health approach to interlink innovations across veterinary and human medicine fields. Full article

Background/Objectives: Physiologically based kinetics (PBK) modelling provides (internal) exposure concentrations. We used a PBK model parameterized exclusively with in silico and in vitro data in a bottom-up approach to predict the pharmacokinetics of oxybenzone, a UV filter, present in two formulations (for which dose-normalized C_max and AUC from clinical studies were different). Methods: Skin absorption data were used to refine chemical-specific dermal absorption parameters for oxybenzone in a lotion and spray. The Transdermal Compartmental Absorption and Transit (TCAT) model in GastroPlus^® 9.9 was used to estimate vehicle and skin layer diffusion and partitioning and then used to simulate systemic exposure. The model was validated according to the OECD 331 guideline. Results: PK profiles simulated for both formulations after single and repeated applications correlated with clinical data profiles (used only to validate our approach), with a deviation from the C_max and AUC of <2-fold. Sensitivity and uncertainty analyses indicated that most input parameters had a medium to high reliability, whereas only a few parameters related to dermal delivery had a low reliability: the partition coefficient between vehicle and water for spray and the diffusion coefficient in stratum corneum for lotion. In vitro skin absorption results suggested that absorption kinetics were not statistically different between the formulations; however, parameters such as vehicle evaporation time were different. The fine-tuned TCAT model containing the absorption data suggested that the variability in clinical data might be due to other factors, e.g., the small number of subjects. Conclusions: These results demonstrate how formulation-dependent absorption kinetics improve confidence in estimated exposure, thanks to the PBK model with its bottom-up approach for nonanimal-based safety assessments. Full article

This review considers L-ascorbic acid as a test substance in designing a dermal drug delivery system for carrying a hydrophilic, low-stability API. Actual studies of nano delivery systems carrying L-ascorbic acid are reviewed. L-ascorbic acid and other antioxidant substances are present in the skin at high levels compared with blood plasma. Augmenting these L-ascorbic acid levels by topical administration may have benefit, but other antioxidants may also need to be augmented. Coadministration of other APIs with L-ascorbic acid may be beneficial, but synergetic interactions are rare and difficult to predict. Some studies reviewed used in vitro methods for quantifying skin retention of API in the living skin layers. These methods may be inadequate. In vivo mouse and rat models suggest therapeutic value of L-ascorbic acid in the skin, but since these animal skins are more permeable than human skin, evidence for good API retention in human skin is weak. Studies using inorganic or polymer nanoparticles for L-ascorbic acid include a lack information concerning skin permeability and retention. Liposome-like systems seem to be the main focus of research now. These studies challenge the understanding of skin penetration mechanisms. Predictions that positively charged deformable liposomes are superior to negatively charged non-deformable liposomes fail. Full article

Wharton’s Jelly-derived mesenchymal stem cell (WJ-MSC) secretome contains diverse bioactive factors with potential for skin regeneration, but its clinical efficacy is limited by poor transdermal delivery. In this study, we developed a dual-delivery system by nanoencapsulating WJ-MSC secretome and coating it onto marine sponge-derived spicules. Physicochemical characterization, in vitro assays (fibroblast and keratinocyte proliferation, keratinocyte migration, type I procollagen secretion, and antioxidant activity), and in vivo penetration studies were conducted. A single-arm clinical trial evaluated dermal absorption, pore characteristics, skin texture, wrinkles, and pigmentation following topical application. Transdermal penetration efficiency was significantly higher in the nano-coated spicule group than in the uncoated secretome control. In vitro, secretome treatment promoted fibroblast and keratinocyte activity, accelerated wound closure, and increased collagen synthesis. Clinically, a single application enhanced dermal absorption and significantly reduced pore number, while two weeks of treatment decreased wrinkles and pigmentation. Spicule-based nanoencapsulation effectively overcomes the skin barrier, enhances the regenerative activity of WJ-MSC secretome, and induces measurable clinical improvements in skin rejuvenation. This platform represents a promising cosmetic and therapeutic strategy in dermatology. Full article

Hydroxypropyl methylcellulose (HPMC) is a biocompatible polymer widely used in topical formulations due to its suitable rheological behavior, film-forming capacity, and good compatibility with different active pharmaceutical ingredients. The present study demonstrates the potential of HPMC-based gels for dermal delivery of porphyrinic photosensitizers, aiming to enhance the efficiency of photodynamic therapy (PDT) in potential skin cancer applications. HPMC-based gel incorporating two previously synthesized porphyrinic photosensitizers, named 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), was developed and carefully characterized regarding its rheological behavior, texture, and in vitro activity. Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), atomic force microscopy (AFM), fluorescence, and UV-Vis spectroscopy were carried out to evaluate the structural and morphological changes induced by the incorporation of the porphyrins in the HPMC gel matrix. The gels were subsequently evaluated by pharmacotechnical analysis, including pH (7.2 for both HPMC-P2.1 and HPMC-P2.2), viscosity, spreadability, texture profile analysis, and drug content uniformity. Rheological behavior confirmed the pseudoplastic behavior, suggesting a structured system with a gel-like consistency, while physical measurements demonstrated the stability and preserved functionality of the photosensitizers within the HPMC matrix. In vitro studies revealed an efficient cellular internalization of selected porphyrins into human epidermoid carcinoma cells, a critical requirement for topical PDT applications. The study highlights the capability of HPMC gels to serve as effective delivery platforms for porphyrin-based photosensitizers, supporting their application in localized skin cancer treatment through PDT. Full article

Octominin is a peptide derived from the Octopus minor defense protein, which has shown antimicrobial and immunomodulatory properties. The present study describes the efficacy of Octominin-encapsulated chitosan (CN) nanoparticles (Octominin-CNPs) on in vitro and dermal wound healing in zebrafish. Initial viability analysis revealed there was no significant toxicity of Octominin-CNPs up to 200 μg/mL in human dermal fibroblast (HDF) cells and in zebrafish larvae (up to 50 μg/mL). Moreover, the potential wound healing activity of Octominin-CNPs was observed using the cell-scratch assay. In the in vivo study, wounded adult zebrafish were applied with the appropriate treatment (PBS, CNPs, Octominin, and Octominin-CNPs) 20 μg/wound/fish as a topical application at 0, 2, and 4 days post-wounding (dpw) while photographs of each wound site were taken at 2, 4, 7, 10, 14, and 21 dpw, and surface area was measured using ImageJ software (Ver. 1.8.0, NIH, Bethesda, MD, USA) to calculate the wound healing percentage (WHP) and wound healing rate (WHR). From the observed results, at 4 dpw, all treatments showed a negative impact on wound healing, where the lowest WHR and the WHP were given by the negative control (NC) until the 14th day. After 7 dpw, all fish except the NC showed increased wound healing activity. Compared to the Octominin, the Octominin-CNPs showed higher activity, which was at its peak on 21 dpw. Furthermore, Octominin-CNPs suppressed the expression of pro-inflammatory cytokine and chemokine mRNA expression with increased wound healing efficacy, and tissue repair compared to the Octominin-alone-treated fish at 7 dpw. Together, the observed results give insights into the use of nanoencapsulation as a means of drug delivery, especially for small peptides. Full article

In recent years, microneedles (MNs), an innovative transdermal drug delivery system, have demonstrated significant advantages in treating diverse skin diseases. The stratum corneum (SC), with its ‘brick-mortar’ structure, is the main barrier to drug penetration into the skin. MNs—including solid, coated, hollow, dissolving, and hydrogel-forming types—penetrate it minimally to form temporary micro-channels, enabling efficient delivery of a wide range of therapeutic agents. These include small molecules, biologics, nanoparticles, and photosensitizers, among others. This technology has been effectively applied in the treatment of androgenetic alopecia, acne, scars, melanoma, psoriasis, atopic dermatitis, and vitiligo. By avoiding stimulation of dermal blood vessels and nerves, MNs offer low pain and high patient compliance. These advantages underscore their broad clinical potential for dermatologic therapy. Future studies must optimize material selection, drug-carrying efficiency, and scale-up production to facilitate clinical translation. Full article

Biocompatible nanofibrous dressings integrating bioactive compounds with antioxidative and antimicrobial properties offer a promising solution for effective wound healing. In the presented study, we developed a novel dual-delivery system by combining forcespun nanofibres with poly(3-hydroxybutyrate) (PHB)-liposomes to enhance bioavailability and enable targeted release of bioactive agents (eugenol, thymol, curcumin, ampicillin, streptomycin, gentamicin). These agents exhibited notable antioxidant activity (2.27–2.33 mmol TE/g) and synergistic or partially synergistic antimicrobial effects against E. coli, M. luteus, S. epidermidis, and P. aeruginosa ( Fractional Inhibitory Concentration index 0.09–0.73). The most potent combinations, particularly thymol, eugenol, and ampicillin, were encapsulated in the nanofibre–liposomal matrix. The successful preparation of a new combined delivery system was confirmed by structural analysis using Electron and Fluorescence Microscopy. The dual-composite materials retained the antimicrobial properties of the individual compounds upon release, with the highest increases of ~73.56% against S. epidermidis. Cell viability and in vitro immunology assays using the human keratinocyte cell line (HaCaT) showed a slight decrease in viability and immune response stimulation, while not impairing wound re-epithelisation. These findings highlight the potential of firstly reported novel carrier utilising both PHB-nanofibres and PHB-liposomes, exhibiting simultaneous antioxidant and antimicrobial activity as promising candidates for the treatment of infected wounds under oxidative stress. Full article

Candida infections pose a significant health threat, and conventional antifungal drugs like nystatin are limited due to poor solubility, skin permeability, and frequent dosage requirements. Nystatin effectively targets Candida species by disrupting cell membranes, but formulation issues hinder clinical use. Lipid-based vesicular carriers, or novasomes, provide controlled, prolonged drug release and enhanced skin penetration. This study focuses on developing nystatin-loaded novasomal gels as an advanced drug delivery system to enhance therapeutic efficacy, bioavailability, and patient compliance. The formulation was prepared using a modified ethanol injection technique, combining stearic acid, oleic acid, Span 60, cholesterol, and Carbopol to produce a stable transdermal gel. Comprehensive in vitro characterization using FTIR, SEM, XRD, and thermal analysis confirmed the chemical compatibility, morphological uniformity, and physical stability of the nystatin-loaded novasomal gel. Entrapment efficiency differed significantly among the formulations (p < 0.05), with F7 achieving the highest value (80%). All formulations maintained pH levels within the skin-friendly range of 5.5 to 7.0. Viscosity measurements, ranging from 3900 ± 110 to 4510 ± 105 cP, confirmed their appropriate consistency for dermal use. Rheological analysis showed a dominant elastic response, as indicated by storage modulus values consistently higher than the loss modulus. Particle size ranged from 4143 to 9570 nm, while PDI values remained below 0.3, reflecting uniform particle distribution. Zeta potential values were strongly negative, supporting physical stability. XRD studies indicated reduced crystallinity of nystatin within the formulations, while FTIR confirmed drug-excipient compatibility. SEM images showed spherical particles within the micrometer range. In vitro release studies demonstrated sustained drug release over 12 h, with F6 releasing the highest amount. The novasomal gel formulations-maintained stability for 30 days, with no notable alterations in pH, viscosity, or entrapment efficiency. Antifungal evaluation showed a larger inhibition zone (23 ± 2 mm) compared with the plain drug solution (15 ± 1.6 mm), while the MIC value was reduced (4.57 µg/mL), indicating greater potency. Skin irritation assessment in rats revealed only minor, temporary erythema, and the calculated Primary Irritation Index (0.22) confirmed a non-irritant profile. These findings suggest that the developed novasomal gel offers a promising approach for enhancing the treatment of fungal infections by enabling prolonged drug release, minimizing dosing frequency, and improving patient compliance. Full article

IGF-1 (insulin-like growth factor 1) is a growth factor primarily secreted by dermal papilla cells on hair-bearing skin that stimulates hair follicle proliferation and vascularization, and promotes the transition to the anagen growth phase of the hair follicle by activating key pathways such as PI3K/Akt and MAPK/ERK. IGF-1 also inhibits apoptosis, prolongs the follicular growth phase, and boosts VEGF expression, which supports microcirculation and nutrient delivery to hair follicles. The combined effects of IGF-1 and other growth factors, including VEGF, KGF (FGF-7), and PDGF, further amplify its effects on follicular cell proliferation and tissue repair. IGF-1’s ability to regulate the hair growth cycle and its interactions with other signaling pathways make it a compelling therapeutic target for hair loss disorders. Both preclinical models and clinical evidence highlight IGF-1 as a promising therapeutic option for conditions like androgenetic alopecia (AGA), where IGF-1 levels are typically diminished. While topical IGF-1 treatments have shown efficacy and safety with minimal systemic absorption, additional research is needed to improve delivery methods, such as liposomal gels and exosome-based carriers, and to evaluate long-term effects. Full article

Background/Objectives: This study presents the development and characterization of a novel thermoresponsive hydrogel composed of hyaluronic acid (HA), poloxamer 407, cannabidiol (CBD), and colloidal silver (Ag), designed for topical antimicrobial therapy. Methods: The Ag-CBD complex was first synthesized and subsequently incorporated into a HA–poloxamer gel matrix to produce a stable, sprayable formulation with suitable physicochemical properties for dermal applications. Results: The HA-Ag-CBD hybrid gel exhibited a physiological pH, a gelation temperature compatible with skin surface conditions, and favorable rheological behavior, including thixotropy and shear thinning—critical for uniform application and retention under dynamic conditions. Release studies confirmed a sustained delivery profile, supporting prolonged local activity of CBD and colloidal Ag. Antimicrobial assays demonstrated that the HA-Ag-CBD hybrid gel retained potent activity against Staphylococcus aureus and Candida albicans, with minimum inhibitory and bactericidal concentrations (MIC/MBC) statistically comparable to those of the unencapsulated Ag-CBD complex. Against E. coli, the HA-Ag-CBD hydrogel exhibited primarily bacteriostatic activity, with a low MIC (9.24 μg/mL) but a substantially higher MBC (387.35 μg/mL), consistent with the intrinsic structural resistance of Gram-negative bacteria. In contrast, bactericidal activity was more pronounced against Gram-positive strains, reflecting differential susceptibility related to bacterial envelope properties. CBD consistently demonstrated superior antimicrobial efficacy to colloidal Ag, while the Ag-CBD combination produced slightly enhanced, mainly additive effects, likely due to complementary membrane disruption and intracellular Ag⁺ ion activity. Cytotoxicity assays on normal human dermal fibroblasts confirmed that the HA-Ag-CBD hybrid gel maintained >70% cell viability at therapeutically relevant concentrations, in accordance with ISO 10993-5:2009 guidelines, and effectively mitigated the inherent cytotoxicity of the Ag-CBD complex. Conclusions: The HA-Ag-CBD hybrid gel demonstrates strong potential as a biocompatible, multifunctional topical formulation for the treatment of infected wounds and skin lesions. Future work will focus on in vivo evaluation, assessment of skin permeation, and further development to support translational applications. Full article

Background: Skin injuries, such as chronic wounds and inflammatory skin diseases, often face limitations in treatment efficacy due to the low efficiency of transdermal drug delivery and insufficient local concentrations. Curcumin (CUR), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated potential in the repair of skin damage; however, its clinical application is hindered by its physicochemical characteristics. This study constructs a novel nanocomposite drug delivery system: CUR-loaded micellar nanocomposite gel (CUR-M-DMNs-Gel). A composite system is used to achieve the efficient solubilization and enhanced transdermal permeation of CUR, thereby providing a novel formulation approach for the treatment of skin diseases. Methods: CUR-loaded micellar (CUR-M) utilizes CUR as the core active ingredient, which possesses multiple pharmacological effects including anti-inflammatory and antioxidant properties. TPGS serves as a micellar carrier that not only enhances the solubility and stability of CUR through its amphiphilic structure but also facilitates drug absorption and transport within the body. In dissolvable microneedles (DMNs), PVP K30 forms a stable three-dimensional network structure through entanglement of polymer chains, ensuring sufficient mechanical strength for effective penetration of the skin barrier. Meanwhile, PVP K90, with its higher molecular weight, enhances the backing’s support and toughness to prevent needle breakage during application. The incorporation of hyaluronic acid (HA) improves both the moisture retention and adhesion properties at the needle tips, ensuring gradual dissolution and release of loaded CUR-M within the skin. In CUR-loaded micellar gel (CUR-M-Gel), PVP K30 increases both adhesive and cohesive forces in the gel through chain entanglement and hydrogen-bonding interactions. Tartaric acid precisely regulates pH levels to adjust crosslinking density; glycerol provides a long-lasting moisturizing environment for the gel; aluminum chloride enhances mechanical stability and controlled drug-release capabilities; NP-700 optimizes dispersion characteristics and compatibility within the system. Results: In vitro experiments demonstrated that the CUR-M-DMNs-Gel composite system exhibited enhanced transdermal penetration, with a cumulative transdermal efficiency significantly surpassing that of single-component formulations. In the mouse skin defect model, CUR-M-DMNs-Gel facilitated collagen deposition and effectively inhibited the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β). In the mouse skin photoaging model, CUR-M-DMNs-Gel markedly reduced dermal thickness, alleviated damage to elastic fibers, and suppressed inflammatory responses. Conclusions: The CUR-M-DMNs-Gel system can enhance wound healing through subcutaneous localization, achieving long-term sustained efficacy. This innovative approach offers new insights into the treatment of skin injuries. Full article