Search Results (436)

Background/Objectives: Burn injuries represent a global public health concern, accounting for approximately 265,000 deaths annually and often leading to severe infections. With the increasing prevalence of multidrug-resistant (MDR) bacteria, innovative therapeutic strategies such as nanoparticle-based topical formulations have gained attention. This study proposed the development of a hydrogel for burn treatment containing biogenic silver nanoparticles (BioAgNPs), hyaluronic acid (HA), and allantoin (AL). Methods: BioAgNPs were previously characterized by transmission electron microscopy (TEM) and incorporated into a hydrogel containing HA and AL, which was physicochemically characterized by pH, spreadability, and energy-dispersive X-ray spectroscopy (EDX). Antibacterial activity was evaluated by broth microdilution, agar diffusion, and time–kill assays against standard and MDR bacterial strains. Cytotoxicity was assessed using the MTT assay in L929 cells, and wound-healing potential was investigated through an in vitro scratch assay to evaluate cell migration and proliferation. Results: BioAgNPs exhibited antibacterial activity against reference strains and MDR isolates, determining the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). HA and AL were non-toxic, while BioAgNPs demonstrated low cytotoxic activity. Although HA and AL did not exhibit antibacterial properties, they promoted cell migration and proliferation. The formulation exhibited physicochemical and pharmaceutical stability, showing suitable properties for topical use, and presented significant antimicrobial action, with bacterial elimination occurring within 2 h of contact, except for S. aureus. Conclusions: Thus, the hydrogel presents a promising alternative for the topical treatment of infected burns, with potential application in combating multidrug-resistant bacteria, being able to eliminate MDR Acinetobacter baumannii. Full article

Acne vulgaris is a prevalent inflammatory disorder of the pilosebaceous unit involving follicular hyperkeratinization, altered sebum production, Cutibacterium acnes proliferation, microbiome imbalance, and immune activation. Although antibiotics, retinoids, benzoyl peroxide, and keratolytic agents remain central to clinical management, their long-term use may be limited by irritation, recurrence, adherence issues, and increasing antimicrobial resistance. This narrative review critically evaluates the dermatological relevance of Melaleuca alternifolia tea tree essential oil (TTEO), Mentha piperita peppermint essential oil (PPEO), and polyhydroxy acids (PHAs), as well as their incorporation into biopolymeric delivery systems for acne-oriented topical applications. Following SANRA principles, evidence from clinical, preclinical, ex vivo, and in vitro studies was synthesized, with emphasis on antimicrobial activity, inflammatory modulation, keratolytic and barrier-supportive effects, formulation stability, and release behavior. TTEO shows the strongest clinical support among the reviewed natural bioactives, including reductions in lesion counts and acne severity when applied as conventional or nanoemulsion-based formulations. PPEO is mainly supported by experimental evidence, particularly antimicrobial activity against acne-associated microorganisms, anti-inflammatory potential, and menthol-related neurocutaneous effects, whereas acne-specific clinical validation remains limited. PHAs, particularly gluconolactone, are better supported for barrier improvement, hydration, tolerability, and seboregulation than for direct acne lesion reduction. Hydrogels, electrospun nanofibers, polymeric films, nanoencapsulation systems, and controlled-release platforms may improve local retention, protect volatile or irritation-prone compounds, and modulate active release at the skin surface. However, most biopolymeric platforms still rely on early-stage or indirect dermatological evidence. Overall, biopolymeric delivery systems offer a rational formulation strategy to improve the stability, tolerability, and localized action of selected acne-relevant bioactives, but their clinical translation requires standardized composition, reproducible fabrication, skin-relevant release assays, safety assessment, and controlled human studies. Full article

The unique anatomy and physiological barriers of the human eye—particularly rapid tear turnover and limited corneal permeability—present significant obstacles to achieving effective topical drug delivery. In response to these constraints, biopolymer-based extended-release systems have emerged as a promising and transformative class of ocular therapeutics. This review provides a comprehensive overview of recent advances in natural biopolymers, including polysaccharides and protein-derived polymers, for application on the ocular surface. These materials exhibit advantageous characteristics such as mucoadhesion, biocompatibility, and stimuli-responsive behavior, which collectively enhance precorneal residence time and enable controlled, sustained drug release. We further discuss diverse delivery platforms—ranging from in situ forming hydrogels and mucoadhesive nanoparticles to drug-eluting contact lenses and microneedle-based systems. In addition, we highlight how the integration of nanotechnology and bioinspired scaffolds can augment the delivery efficiency of therapeutic agents to ocular tissues. Overall, this review underscores the ongoing transition from conventional topical eye drops to sophisticated, functionalized delivery systems capable of maintaining therapeutic drug levels while simultaneously supporting tissue repair and wound healing. Finally, we outline the remaining challenges in clinical translation and consider the future potential of smart, responsive biopolymer systems in advancing the treatment of both anterior and posterior segment diseases. Full article

Background/Objectives: The increasing emergence of antimicrobial-resistant Staphylococcus pseudintermedius has limited the effectiveness of conventional therapies for canine pyoderma, highlighting the need for alternative topical strategies. This study aimed to develop hydrogels incorporating essential oils (EOs) from Peumo (Cryptocarya alba) and Tepa (Laureliopsis philippiana) as potential topical treatments against Staphylococcus pseudintermedius skin infections in veterinary medicine. Methods: EOs were obtained by steam distillation, chemically characterized by gas chromatography–mass spectrometry (GC–MS), and evaluated for antibacterial activity against S. pseudintermedius strains. Carbopol^®-based hydrogels incorporating the EOs of C. alba (HCA), L. philippiana (HLP), and a control vehicle (HVE) were formulated and characterized in terms of physicochemical properties, microbiological safety, and stability under accelerated and refrigerated conditions. Preclinical dermal safety was evaluated in BALB/c mice by repeated topical administration for five days. The analysis included clinical observation, skin irritation scoring, and histological analysis. Additionally, a preliminary microbiological evaluation was conducted in client-owned dogs with superficial pyoderma to assess the performance of the formulations in the target species. Skin lesion swabs were collected at baseline and after 21 days of treatment, followed by bacterial culture and automated identification using the VITEK^® system. Bacterial detection and bacterial load were evaluated to determine changes in microbiological status over the treatment period. Results: GC–MS analysis identified sabinene and eucalyptol as the main compounds in CA-EO, and linalool, eucalyptol, and safrole in L. philippiana EO. Both EOs exhibited moderate antibacterial activity against S. pseudintermedius (inhibition zones 4.9–10.8 mm; MIC ≥ 2.048 mg mL⁻¹). The hydrogels were microbiologically safe. Among formulations, HLP demonstrated superior physical stability and comparable rheological properties to the vehicle. In vivo safety evaluation demonstrated no signs of systemic toxicity, behavioral alterations, or skin irritation, and histological analysis confirmed preserved skin architecture without evidence of inflammation or tissue damage. In the preliminary microbiological evaluation in dogs, all animals were positive for Staphylococcus spp. at baseline. On Day 21, bacterial elimination was observed in the active treatment groups, but not in the HVE group, with elimination rates of 50.0% for Inveclor^® and 25.0% for both HCA and HLP. In parallel, HLP showed the highest proportion of dogs reaching minimal bacterial load levels (75%), followed by Inveclor^® (50.0%) and HCA (37.5%), whereas no dogs in the vehicle group reached this category. Conclusions: EOs from C. alba and L. philippiana presented antibacterial activity and were successfully incorporated into microbiologically safe hydrogel formulations. Notably, HLP demonstrated superior stability and a favorable preclinical safety profile, supporting its potential. In the preliminary microbiological evaluation in dogs, numerical differences in bacterial elimination and bacterial load categories were observed among groups; however, these differences were not statistically significant and should be interpreted as exploratory. Full article

Background/Objectives: Cannabis sativa is the source of cannabidiol (CBD), a non-intoxicating phytocannabinoid with analgesic and anti-inflammatory qualities that has demonstrated therapeutic potential in inflammatory skin conditions like dermatitis. However, low bioavailability and poor water solubility restrict its topical application. This study attempted to improve CBD solubility and transdermal delivery using an amorphous solid dispersion (ASD)-based hydrogel system. Methods: CBD was stabilized in its amorphous form using an ASD strategy and incorporated into a hydrogel matrix. The CBD-ASD hydrogel was characterized by particle size analysis, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), rheological assessment, swelling studies, and diffusion experiments using Franz cells. Biological evaluations included cytotoxicity testing in human dermal fibroblast (HDF) cells, wound-healing assays, RT-qPCR-based anti-inflammatory analysis, antioxidant activity (DPPH assay), and antibacterial testing against Staphylococcus aureus. Results: Physicochemical analyses confirmed successful amorphous dispersion of CBD within a stable hydrogel network. The formulation exhibited sustained drug release over 144 h, achieving 86.32% cumulative release with diffusion-controlled kinetics. Rheological and swelling properties demonstrated mechanical stability and hydration suitability for long-term topical application, while Franz diffusion studies confirmed effective transdermal permeation. The CBD-ASD hydrogel showed no cytotoxicity in HDF cells and significantly enhanced wound closure. It also downregulated pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Additionally, the formulation demonstrated 65.63 ± 10.00% DPPH radical scavenging activity and over 99% antibacterial inhibition. Conclusions: The CBD-ASD hydrogel represents a stable, multifunctional delivery platform that overcomes CBD solubility limitations and enhances therapeutic efficacy for inflammatory skin diseases. Full article

Polymer-based dressings constitute an important class of macromolecular biomaterials enabling controlled drug delivery and enhanced wound healing performance. This review summarizes recent advances in the design, fabrication, and functionalization of polymer dressings, with emphasis on natural and synthetic polymer systems applied in biomedical topical and transdermal drug administration. Key material properties, including biocompatibility, mechanical stability, porosity, and degradation behavior, are discussed in relation to drug loading capacity and release kinetics. Current fabrication strategies, such as electrospinning, hydrogel formation, casting, and multilayer assembly, are critically evaluated with respect to structural control and scalability. Particular attention is given to antimicrobial and stimuli-responsive platforms capable of dynamic interaction with the wound microenvironment. Furthermore, challenges related to long-term stability, regulatory requirements, and clinical translation are addressed. By integrating recent experimental findings, this review highlights essential structure–function relationships governing polymer dressing performance and provides design guidelines for next-generation macromolecular topical and transdermal care systems with improved multifunctionality and clinical applicability. Full article

Background: Diabetic foot ulcers (DFUs) are difficult to heal because hyperglycemia-associated pathological exudation, excessive oxidative stress, chronic inflammation, and impaired cellular regeneration jointly maintain a nonhealing wound microenvironment. This study aimed to develop and evaluate a composite hydrogel containing Periplaneta americana (PA) extract and calamine as a Zn²⁺ source for dynamic modulation of the diabetic wound microenvironment and promotion of tissue repair. Methods: A PA composite hydrogel was prepared and assessed in vitro for reactive oxygen species (ROS)-scavenging activity and effects on fibroblast migration. Therapeutic efficacy was further evaluated in a streptozotocin (STZ)-induced diabetic full-thickness wound model in rats. Wound closure, histological remodeling, oxidative stress markers, inflammatory mediators, growth factors, angiogenesis, and AGEs-RAGE/NF-κB pathway-related changes were analyzed. Results: The composite hydrogel reduced excessive intracellular ROS and enhanced fibroblast migration in vitro compared with pathological-condition controls. In diabetic rats, topical treatment accelerated macroscopic wound closure and promoted more mature histological repair. Mechanistic analyses showed attenuation of the AGEs-RAGE/NF-κB signaling axis, accompanied by restoration of superoxide dismutase activity, reduction of malondialdehyde levels, and suppression of TNF-α-associated inflammatory responses. The improved wound microenvironment was associated with increased expression of platelet-derived growth factor and basic fibroblast growth factor, enhanced cellular proliferation, and increased neovascularization within the wound tissue. Conclusions: The PA composite hydrogel improved diabetic wound healing by concurrently alleviating oxidative and inflammatory barriers and enhancing regenerative signaling. These findings suggest that microenvironment-modulating PA composite hydrogel systems may represent a promising therapeutic strategy for refractory diabetic wounds. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

Background/Objectives: Thermal injuries represent a significant global health burden, often complicated by hypertrophic scarring, chronic inflammation, and delayed re-epithelialization. While Mesenchymal Stem Cell (MSC) transplantation has shown promise, its clinical translation is hindered by risks of tumorigenicity and immunological concerns. This study evaluates the efficacy of cell-free Extracellular Vesicle (EV) therapy—derived from both mammalian MSCs and plant sources (PDNVs)—as standardized, off-the-shelf alternatives. This study synthesizes evidence focusing on re-epithelialization velocity, angiogenic activity, and anti-fibrotic outcomes, while assessing the impact of second-generation delivery scaffolds on therapeutic durability. Methods: Conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261305379), this review interrogated PubMed, Scopus, Embase, and Web of Science for studies published between 2015 and 2026. Eligible studies included in vivo animal models of thermal injury using purified vesicles from mammalian MSC sources or plant-derived nanovesicles compared with placebo, standard care, or untreated controls. Data were synthesized narratively; methodological quality was appraised using the SYRCLE risk of bias tool and compliance with MISEV guidelines. Results: Synthesis of 50 studies revealed that vesicle-based interventions consistently accelerate wound closure and improve histological healing. Mammalian ADSC-derived vesicles demonstrated superior anti-fibrotic effects via the miR-192-5p and miR-125b-5p axes, while hUC-MSC vesicles attenuated systemic inflammatory signaling via miR-181c. Plant-derived nanovesicles (PDNVs) showed potent antioxidant and re-epithelialization effects, with emerging potential as engineered genetic carriers. Crucially, advanced delivery systems, including bioactive hydrogels and microneedle patches, were repeatedly associated with improved local retention and more durable effects than bolus injections. Conclusions: Vesicle-based therapies show consistent pro-healing signals in preclinical models, suggesting source-dependent profiles: MSC-derived vesicles excel in immunomodulation and anti-fibrotic remodeling, while PDNVs provide a scalable, low-immunogenicity platform. As a cell-free strategy, these therapies circumvent the safety risks of live cell transplantation. This review identifies a critical shift toward second-generation delivery scaffolds to overcome the clearance crisis of topical applications, emphasizing the need for harmonized MISEV-aligned characterization in future clinical translation. Full article

Due to their availability and environmental friendliness, alginate polymers are widely used in pharmaceuticals and cosmetics. The most common type of alginate is derived from seaweed and is used to develop topical dosage forms, among other things. However, variability in the seaweed material can lead to instability in the physicochemical parameters. Biotechnologically produced alginate minimizes this drawback through controlled synthesis. However, unlike algal alginates, the safety profile of such polymers has not been well studied. When developing dosage forms intended for wound surfaces, safety is of primary importance. In this study, we developed enzybiotic compositions based on bacterial alginate as an excipient and a novel recombinant modified endolysin, LysSi3-LK, as an antibacterial agent, and assessed their antibacterial properties and safety profile. The study included an in vitro evaluation of the activity spectrum, as well as the cytotoxicity and biocompatibility, of gel and hydrogel compositions. It was demonstrated that bacterial alginate is acceptable for the encapsulation of endolysin. It exhibited medium cytotoxic effects on the HaCaT cells, which were significantly reduced by the LysSi3-LK addition. The migration of cells was diminished following exposure to the gel and hydrogel formulations. However, an improvement in biocompatibility was observed in the cell proliferation assay. Full article

Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus = 1:1, each at 1 × 10⁷ CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), and IL-1β (interleukin-1 beta) was significantly decreased, the mRNA expression of ZO-1 (zonula occludens-1), Occludin, and Claudin-4 was significantly increased, and Bax/Bcl-2 (Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p < 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment. Full article

Ultraviolet B (UVB), as a major component of solar radiation, is a key factor in inducing skin photoaging. The epidermis serves as the primary defensive barrier of the skin and absorbs the majority of UVB. This study aims to elucidate the protective effect of Alk against UVB-induced photoaging and further uncover its underlying molecular mechanisms. In vitro, Alk-pretreated HaCaT cells were exposed to UVB. Cell viability, ROS, senescence, antioxidant enzymes, and protein expression were analyzed. Mechanisms were examined using CETSA, DARTS, Co-IP, and NRF2 knockout. In vivo, Alk hydrogel was tested in UVB-exposed BALB/c mice, with protection assessed via histology and immunohistochemistry. In vitro, Alk directly binds to Keap1, disrupts Keap1–Nrf2 interaction, promotes nuclear translocation of Nrf2, and upregulates the expression of its downstream target HO-1. Consequently, intracellular ROS generation is reduced, cellular senescence is alleviated, and the expression of inflammatory factors (TNF-$\alpha$, COX-2) and MMP-9 is suppressed. In vivo, topical application of the Alk hydrogel prevented UVB-induced skin thickening and collagen degradation. Alk exerts a preventive effect on UVB-induced photoaging in HaCaT cells and skin, providing strong support for developing Alk as a potential plant-derived active ingredient for preventing skin photoaging. Full article

The development of effective topical drug delivery systems remains a key challenge in wound management, particularly for bioactive compounds with limited skin permeability. In this study, a nanostructured bigel system incorporating sodium humate-loaded ultra-deformable vesicles (UDVs) was developed and evaluated for wound healing applications. Sodium humate-loaded UDVs were prepared using a thin-layer hydration method, and the influence of key technological parameters (phospholipid/glycerol concentrations, sonication time) on vesicle size and encapsulation efficiency was investigated. An optimized UDV formulation characterized by small particle size, high stability, and high drug encapsulation efficiency was selected and incorporated into a bigel composed of hydroxypropyl methylcellulose hydrogel and andiroba oil oleogel. The developed bigels were characterized in terms of microstructure, physical stability, pH, spreadability, and rheological behavior, demonstrating suitable properties for dermal application. In vivo wound healing evaluation in rat wound models revealed that bigels containing sodium humate-loaded UDVs significantly enhanced wound closure and tissue regeneration compared to control and reference treatments. Histopathological analysis confirmed improved granulation tissue formation and complete epithelialization. Overall, the results demonstrate that the proposed UDV-loaded hybrid bigel represents a promising nanostructured platform for enhanced dermal delivery and wound healing therapy. Full article

Olive mill wastewater (OMW) is an agro-industrial byproduct rich in polyphenols and other bioactive compounds with documented antioxidant and antimicrobial properties. In this study, purified OMW fractions (RO1 and MD2), previously characterized by high polyphenol content and strong antioxidant activity, were incorporated (10% w/w) into cellulose-based hydrogels intended for topical application. Hydrogels were prepared using carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), and methylcellulose (MC) at concentrations of 1.5–2.0% (w/w). The formulations were characterized in terms of organoleptic properties, pH, rheological behavior, swelling capacity, weight loss, antioxidant activity (DPPH assay), and microbiological activity against selected skin pathogens, including antibiotic-resistant strains. Rheological analysis confirmed pseudoplastic behavior suitable for topical administration. OMW-loaded hydrogels exhibited significant radical scavenging activity compared to blank formulations and demonstrated antimicrobial efficacy, supporting the preservation of OMW bioactivity within the polymeric network. The results highlight the potential of cellulose-based hydrogels as sustainable and biocompatible carriers for the valorization of OMW in dermatological applications, particularly for the management of oxidative stress and bacterial skin infections. Full article

Background: Post-episiotomy wound healing remains largely managed through supportive care, despite growing evidence that local biochemical conditions critically influence tissue regeneration. Lactic acid is of particular interest in this context because it is both an endogenous metabolic intermediate and a physiologic component of the vaginal microenvironment, where it contributes to acidic pH maintenance, microbial homeostasis, and mucosal protection. Beyond these local effects, lactate has emerged as a signaling metabolite involved in angiogenesis, immune regulation, and extracellular matrix remodeling, making it a relevant candidate for regenerative wound care. Methods: This narrative translational review integrates evidence from molecular biology, biomaterials science, and clinical obstetrics to examine the therapeutic potential of lactic acid-loaded hydrogels for post-episiotomy tissue repair. Literature from PubMed, Scopus, and Web of Science was analyzed to evaluate physicochemical design parameters, lactate-mediated signaling pathways, and available clinical outcomes. Results: Lactic acid may function both as a microenvironmental regulator and as a metabolic signal capable of stabilizing hypoxia-inducible factor-1α signaling, enhancing vascular endothelial growth factor expression, modulating macrophage polarization, and influencing fibroblast-mediated extracellular matrix synthesis. Hydrogel matrices provide tunable platforms for controlled lactate release, pH buffering, and mucosal compatibility. Clinical studies suggest improved epithelialization, reduced infection risk, and lower pain scores following topical lactic acid formulations in episiotomy repair. In parallel, platelet-rich plasma provides autologous growth factor enrichment that may complement regenerative signaling pathways. Conclusions: Integrating microenvironment stabilization through lactic acid-based hydrogels with biologically active regenerative strategies represents a promising direction for post-episiotomy wound healing. Further controlled trials and standardized biomaterial characterization are required to define optimal therapeutic protocols and confirm long-term clinical benefit. Full article