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Search Results (223)

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Keywords = dermal delivery system

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29 pages, 41563 KB  
Article
Paeonol-Loaded Cyclodextrin/Composite Hydrogel for Enhanced Transdermal Delivery and Skin Photoaging Repair
by Xinrui Chen, Yong Liu, Ruofei Zu, Wenwen Li, Xueer Wang, Xinyi Yang, Chuanji Zhu, Yuling Xu, Ziwen Xie and Hongmei Xia
Gels 2026, 12(8), 746; https://doi.org/10.3390/gels12080746 - 20 Aug 2026
Abstract
Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based [...] Read more.
Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based on a carboxymethyl chitosan (CMCS)/Carbomer 940 (Carb940) composite gel loaded with hydroxypropyl-β-cyclodextrin inclusion complexes of paeonol (Pae-CD) was developed. Pae-CD was prepared using an ultrasound-assisted saturated aqueous solution method, and the physicochemical properties, sustained-release behavior, transdermal permeation, antioxidant activity, and safety of Pae-CD/gel were evaluated. Furthermore, a mouse model of skin photoaging induced by combined ultraviolet A (UVA)/ultraviolet B (UVB) irradiation was established to investigate its reparative effects in vivo. The results showed that Pae-CD/gel exhibited a homogeneous three-dimensional porous structure, favorable sustained-release characteristics, enhanced skin retention capacity, and good cellular compatibility. In vivo experiments demonstrated that Pae-CD/gel markedly ameliorated ultraviolet-induced skin dryness, abnormal epidermal thickening, and dermal collagen loss. It also reduced oxidative stress and inflammatory factor levels, down-regulated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) expression, and promoted the restoration of collagen type I (COL-1) and hydroxyproline (HYP) levels. Systemic safety evaluation revealed no obvious toxicity. In summary, Pae-CD/gel exerts antioxidant and anti-inflammatory effects and regulates collagen metabolism by enhancing transdermal delivery and local retention, thereby providing a safe and effective topical delivery strategy for the repair of skin photoaging. Full article
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18 pages, 2605 KB  
Article
Influence of Lipid Matrix Composition on the Intestinal Permeation of Curcumin-Loaded Lipid Nanoparticles
by Anam Sajjad Khan, Daniela Müller and Cornelia M. Keck
Pharmaceutics 2026, 18(8), 1024; https://doi.org/10.3390/pharmaceutics18081024 - 18 Aug 2026
Viewed by 136
Abstract
Background: Lipid nanoparticles are widely investigated as oral drug delivery systems, but their intestinal performance remains difficult to predict based only on physicochemical properties. This study aimed to elucidate how the lipid matrix composition influences the intestinal permeation of curcumin from lipid nanoparticles. [...] Read more.
Background: Lipid nanoparticles are widely investigated as oral drug delivery systems, but their intestinal performance remains difficult to predict based only on physicochemical properties. This study aimed to elucidate how the lipid matrix composition influences the intestinal permeation of curcumin from lipid nanoparticles. Methods: Curcumin-loaded nanoemulsions, nanostructured lipid carriers with defined solid-to-liquid lipid ratios, and solid lipid nanoparticles were prepared by high-pressure homogenization. All formulations were characterized with respect to particle size, polydispersity index, and zeta potential before and after simulated intestinal pre-incubation in a simplified SDS-containing intestinal fluid. Intestinal permeation was evaluated ex vivo using porcine gut tissue by analysis of semi-quantitative fluorescence-based permeation readouts (ART) and mean permeation depth (MPD) after 30 and 60 min. Results: All formulations maintained stable physicochemical properties with particle sizes around 200 nm and negative zeta potentials; pre-incubation increased the negativity of the zeta potential but left particle size unchanged. Despite similar attributes, the formulations differed in intestinal curcumin permeation based on time and composition. At 30 min, nanoemulsions and mixed nanostructured lipid carriers achieved the highest performance. By 60 min, lipid carriers with more liquid lipid significantly increased both the fluorescence intensity and the depth of curcumin permeation, while other systems showed little further improvement. Conclusions: The intestinal permeation of drug from lipid nanoparticles is governed by the lipid matrix architecture and its interaction with the hydrated intestinal environment, which together affect drug-release kinetics and the ability to sustain a trans-epithelial concentration gradient over time. Thus, optimizing oral lipid nanoparticles requires time-resolved, biologically relevant models rather than physicochemical characterization alone, consistent with observed similar matrix-driven effects in dermal delivery systems. Full article
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15 pages, 795 KB  
Review
Pyrroloquinoline Quinone (PQQ) as a Mitochondrial Rejuvenation Strategy in Aesthetic Dermatology: Mechanisms, Therapeutic Potential, and Future Clinical Applications
by Kyu-Ho Yi
Biomolecules 2026, 16(8), 1197; https://doi.org/10.3390/biom16081197 - 17 Aug 2026
Viewed by 224
Abstract
Background: Mitochondrial dysfunction is increasingly recognized as a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that has attracted interest because [...] Read more.
Background: Mitochondrial dysfunction is increasingly recognized as a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that has attracted interest because it can participate in repeated redox cycling, protect mitochondrial function, and activate signaling associated with mitochondrial biogenesis. Objective: This narrative review evaluates the mechanistic basis, available dermatologic evidence, translational opportunities, and major uncertainties surrounding PQQ as a mitochondrial rejuvenation strategy in aesthetic dermatology. Methods: PubMed/MEDLINE and Europe PMC were searched from database inception through 10 August 2026 using PQQ-, mitochondrial-, skin-, delivery-, and safety-related terms; reference lists were also screened. Mechanistic, preclinical, skin-focused, human, and regulatory evidence was synthesized narratively. Results: Experimental studies support PQQ-mediated activation of mitochondrial biogenesis pathways and protection against oxidative injury in several cell and animal systems. Skin-specific evidence includes attenuation of oxidative stress, DNA damage, senescence markers, and matrix metalloproteinases in accelerated-aging mouse models; protection of UVA-exposed human dermal fibroblasts; suppression of UVB-induced caspase-1 release in keratinocytes; a small oral dry-skin study; and a multi-ingredient topical study containing an allyl PQQ derivative. These studies do not establish PQQ-specific clinical aesthetic efficacy. Conclusion: PQQ is a biologically plausible mitochondrial-support compound, but it should currently be regarded as an investigational ingredient rather than an established aesthetic treatment. Carefully designed formulation, toxicology, dose-finding, biomarker, and randomized clinical studies are required before claims regarding wrinkle reduction, pigment improvement, enhanced collagen production, or accelerated post-procedure recovery can be justified. Full article
(This article belongs to the Special Issue Bioactive Compounds in Dermatology)
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73 pages, 20310 KB  
Review
Polymeric Nanocarriers and Polymer-Assisted Delivery Platforms for Oleanolic Acid: Design Strategies, Controlled Release, Translational Challenges, and Clinical Perspectives
by Andrzej Günther and Barbara Bednarczyk-Cwynar
Micromachines 2026, 17(8), 944; https://doi.org/10.3390/mi17080944 - 7 Aug 2026
Viewed by 553
Abstract
Oleanolic acid is a naturally occurring pentacyclic triterpenoid with broad preclinical promise in inflammation, oxidative stress, liver injury, metabolic disorders, cancer-related models, skin disease, and wound repair. Its further development, however, is constrained by poor aqueous solubility, low and variable bioavailability, limited barrier [...] Read more.
Oleanolic acid is a naturally occurring pentacyclic triterpenoid with broad preclinical promise in inflammation, oxidative stress, liver injury, metabolic disorders, cancer-related models, skin disease, and wound repair. Its further development, however, is constrained by poor aqueous solubility, low and variable bioavailability, limited barrier transport, crystallinity, and strong dependence of biological response on the formulation used. These properties make oleanolic acid a useful example of a hydrophobic natural compound whose pharmacological performance is inseparable from delivery design. This review examines polymeric nanocarriers and polymer-assisted delivery platforms developed for oleanolic acid delivery. Polymeric nanocarriers discussed in the review include biodegradable PLA/PLGA nanoparticles, PEGylated polymeric nanoparticles, polymeric micelles, nanogels, hyaluronic-acid-based nanoprodrugs, and selected polymer-assisted hybrid nanostructures. Hydrogels, polymeric fiber membranes, local depots, and microneedle systems are included as route-enabling delivery platforms when the polymeric matrix directly contributes to OA incorporation, carrier stabilization, local retention, barrier bypass, or release control. Non-polymeric delivery systems are discussed only as comparators or when their performance depends on integration with a polymeric component. Rather than treating these carriers only as solubility enhancers, the review evaluates how polymer composition, carrier architecture, drug physical state, release behavior, and route of administration affect oleanolic acid exposure. Particular attention is given to controlled release, local retention, disease-oriented delivery, and critical quality attributes such as particle size, loading, encapsulation efficiency, solid-state form, stability, residual solvent, sterility, and batch-to-batch reproducibility. Representative quantitative data on carrier size, drug loading, encapsulation efficiency, release, stability, tissue exposure, and biological outcomes are compared to illustrate both formulation-specific performance and the substantial methodological heterogeneity of the available studies. The available evidence indicates that increased apparent solubility, increased biological exposure, and improved therapeutic response should be treated as related but distinct outcomes. The most realistic near-term opportunities may lie in local and tissue-targeted applications, including inflammatory skin disease, wound healing, dermal delivery, and osteoarthritis, where sustained target-site exposure may be more relevant than systemic bioavailability. Future progress will depend on demonstrating that each formulation provides reproducible, safe, and route-appropriate OA exposure, together with a measurable advantage over simpler delivery approaches. Full article
(This article belongs to the Section B5: Drug Delivery System)
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24 pages, 2243 KB  
Article
Niosomal Encapsulation of Oroxylum indicum Leaf Extract for Topical Anti-Inflammatory Application
by Pattaraphorn Panomai, Nattawadee Kanpipit, Natsajee Nualkaew and Suthasinee Thapphasaraphong
Pharmaceutics 2026, 18(8), 955; https://doi.org/10.3390/pharmaceutics18080955 - 3 Aug 2026
Viewed by 364
Abstract
Background: Oroxylum indicum (L.) Kurz is a medicinal plant widely used in traditional Thai medicine, reported to exhibit anti-inflammatory activity. However, its topical use is limited by the poor dermal delivery of its active compounds. This study aimed to develop and characterize [...] Read more.
Background: Oroxylum indicum (L.) Kurz is a medicinal plant widely used in traditional Thai medicine, reported to exhibit anti-inflammatory activity. However, its topical use is limited by the poor dermal delivery of its active compounds. This study aimed to develop and characterize a topical niosomal delivery system containing O. indicum leaf extract to enhance permeation through Strat-M® membrane and anti-inflammatory activity. Methods: Extract-loaded niosomes were prepared via thin-film hydration using non-ionic surfactants and cholesterol. The developed niosomes were evaluated for their physicochemical properties, in vitro release and in vitro permeation, stability, and anti-inflammatory effects in LPS-stimulated RAW 264.7 cells. Results: The optimal formulation consisted of a phosphate buffer at pH 5.5, Span 60, cholesterol, 0.5% (w/v) extract, and 10% propylene glycol, with the extract added during the hydration step. The optimal formulation showed a high encapsulation efficiency (>70% (total phenolics) and >90% (total flavonoids), a nano-sized particle size of approximately 100–200 nm with a narrow size distribution, and a zeta potential within the acceptable value (≤−30 mV). The successful incorporation of the extract into niosome bilayers was confirmed by FTIR spectroscopy. The niosomal formulation demonstrated a significantly more sustained and controlled release of total phenolics and flavonoids, including enhanced permeation of phenolic compounds across the Strat-M® membrane, compared to the extract solution. Formulations containing 0.3–0.5% extract remained physically stable, maintaining encapsulation efficiency, particle size, and zeta potential under thermal stress conditions. Significantly, niosomes loaded with 0.5% extract exhibited the greatest inhibition of nitric oxide production in RAW 264.7 cells without cytotoxicity. Conclusions: These findings are based on in vitro membrane permeation and cell-based assays; further ex vivo or in vivo skin studies are required to confirm topical anti-inflammatory efficacy. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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39 pages, 8463 KB  
Review
Intelligent Hydrocolloid-Based Delivery Systems: Innovations in Pharmacy and Cosmetics
by Karen Khachatryan, Oskar Michalski and Klaudia Michalska
Molecules 2026, 31(14), 2468; https://doi.org/10.3390/molecules31142468 - 15 Jul 2026
Cited by 1 | Viewed by 865
Abstract
Hydrocolloid-based and hydrocolloid-dominant hybrid matrices have developed from conventional rheology modifiers into functional platforms for pharmaceutical and cosmetic delivery. This review focuses on systems in which hydrocolloid chemistry, hydration, ionisation, bioadhesion, and network architecture determine swelling, mechanical behaviour, biocompatibility, and controlled release. The [...] Read more.
Hydrocolloid-based and hydrocolloid-dominant hybrid matrices have developed from conventional rheology modifiers into functional platforms for pharmaceutical and cosmetic delivery. This review focuses on systems in which hydrocolloid chemistry, hydration, ionisation, bioadhesion, and network architecture determine swelling, mechanical behaviour, biocompatibility, and controlled release. The discussion covers alginate, chitosan, hyaluronic acid, pectin, carrageenan, dextran, gellan gum, collagen, cellulose derivatives, and selected hybrid architectures in which synthetic or semi-synthetic components provide a defined responsive function. Rather than treating all smart polymers as a single class, the review compares how pH, enzymatic, redox/ROS, thermo-responsive, magnetic, optical, ultrasound-mediated, and multi-trigger mechanisms operate within hydrocolloid-rich matrices. Pharmaceutical examples are considered across oral, transdermal, injectable depot, wound-healing, and regenerative applications, while cosmetic and cosmeceutical systems are discussed in relation to active stabilisation, dermal residence, barrier support, and personalised skincare. By linking material class, trigger mechanism, route of administration, and translational constraints, the review identifies the main advantages of hydrocolloids as delivery matrices as well as their current limitations, including burst release, modest mechanical strength, hydrophobic-drug loading challenges, sterilisation sensitivity, source variability, and regulatory complexity. Full article
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18 pages, 3510 KB  
Article
In Vitro and Ex Vivo Studies on the Absorption and Distribution of β-Cyclodextrin Polymer
by Réka Révész, Akay Dogan Mengenli, Ágnes Rusznyák, Richárd Kajtár, István Lekli, Ildikó Bácskay and Ádám Haimhoffer
Pharmaceutics 2026, 18(7), 854; https://doi.org/10.3390/pharmaceutics18070854 - 14 Jul 2026
Viewed by 362
Abstract
Background: Cyclodextrin (CD) polymers have attracted increasing attention due to their favourable drug delivery properties and broad pharmaceutical applicability. While the bioavailability and biological behaviour of native cyclodextrins have been extensively investigated, considerably less information is available regarding modified cyclodextrin polymers. Therefore, [...] Read more.
Background: Cyclodextrin (CD) polymers have attracted increasing attention due to their favourable drug delivery properties and broad pharmaceutical applicability. While the bioavailability and biological behaviour of native cyclodextrins have been extensively investigated, considerably less information is available regarding modified cyclodextrin polymers. Therefore, the present study aimed to investigate the permeation and cellular uptake of an epichlorohydrin-crosslinked β-cyclodextrin polymer using multiple in vitro and ex vivo models. Methods: Fluorescently labelled β-cyclodextrin polymers were applied in all experiments. Membrane permeation studies were performed using an in-line diffusion cell system with membranes of different pore sizes. In vitro transport and cellular uptake were investigated on HaCaT, Caco-2, and TR146 cell monolayers, while ex vivo permeation studies were carried out using skin, buccal, and intestinal tissues. Results: The results demonstrated a strong size-dependent transport behaviour across synthetic membranes. Cell monolayer studies revealed cell-line-dependent differences in polymer intracellular distribution. Lysosomal accumulation was observed in HaCaT and Caco-2 cells, whereas no intracellular accumulation was detected in TR146 cells. These findings suggest differences in polymer permeation among the investigated cell models. Ex vivo studies demonstrated the tissue permeation of cyclodextrin polymers, with marked accumulation within skin layers, indicating predominant dermal retention. Furthermore, strong correlations were identified between the in vitro and ex vivo skin and intestinal models. Conclusions: Overall, the findings demonstrate that β-cyclodextrin polymers exhibit complex, barrier-dependent transport behaviour across different biological models. The observed differences in permeation and intracellular localization suggest that multiple transport processes may contribute to their biological interactions, which provide a foundation for future studies aimed at elucidating the molecular mechanisms governing polymer uptake and permeation. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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32 pages, 3007 KB  
Review
Nanotechnologies for Skin Drug Delivery: Polymeric, Bio-Based, and Hybrid Nanocarriers with Clinical and Translational Perspectives
by Lina Eltaib, Hamoud Alotaibi, Mona Al Hamod, Saleh Alfuraih, Noura Al Hamood, Ahmad Mohammad Balkhair and Abdullah Abdulrahman Aljasser
Pharmaceuticals 2026, 19(7), 1057; https://doi.org/10.3390/ph19071057 - 8 Jul 2026
Viewed by 720
Abstract
The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often [...] Read more.
The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments. Full article
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19 pages, 1800 KB  
Article
Beyond Nano-Delivery: Synerjet-Assisted Transdermal Delivery of Nano-Formulated Nicotinamide Mononucleotide (Nano-NMN) for Comprehensive Skin Rejuvenation
by Wonkyu Hong, Jaewoo Kim, Seongmin Noh, Joonho Shim, Seok-Kwang Park and Mihwa Kim
Cosmetics 2026, 13(4), 172; https://doi.org/10.3390/cosmetics13040172 - 3 Jul 2026
Viewed by 929
Abstract
This study aimed to evaluate whether the Synerjet system can maximize the transdermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n = 21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced [...] Read more.
This study aimed to evaluate whether the Synerjet system can maximize the transdermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n = 21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced improvements in wrinkles (with 170.56% relative improvement in periorbital and 154.45% in nasolabial region compared to the control group), pore volume (176.62%), and deep hydration (188.02%). Regarding dermal integrity, the test group showed a 111.56% superior increment in skin elasticity and a 149.75% more effective optimization of melanin intensity relative to the control. Notably, deep-tissue hydration at a 2.5 mm depth demonstrated a 188.02% higher gain, suggesting that the modality significantly fortifies the skin’s physiological moisture reservoir. The test group exhibited a marked improvement over the control across all cutaneous parameters (p < 0.001). Our findings demonstrate that a new combinatorial approach using EP-assisted microjet of a Synerjet system after cold plasma pretreatment and a nano-NMN 10% ampoule resulted in significantly greater improvements in wrinkles, pores, elasticity, pigmentation, and deep skin hydration compared to topical application alone. Consequently, these results demonstrated that the Synerjet system effectively overcame the inherent limitations of nano-delivery technologies, offering a promising modality for advanced cutaneous rejuvenation and a robust framework for future professional dermatological treatments. Full article
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26 pages, 8462 KB  
Article
Evaluation of Functional Electrospun Chitosan-Based Nanofibers Loaded with Norfloxacin for Enhanced Burn Wound Healing Response
by Corneliu-George Coman, Ioannis Gardikiotis, Carmen Solcan, Cosmin-Gabriel Tartau, Caroline Chabot, Gianina Dodi and Liliana Mititelu Tartau
Polymers 2026, 18(13), 1621; https://doi.org/10.3390/polym18131621 - 30 Jun 2026
Viewed by 487
Abstract
Nanofibrous materials based on chitosan (CS) have attracted considerable attention for advanced wound management due to their excellent biocompatibility and their suitability as drug delivery systems for wound healing applications. Additional surface modification may improve their interaction with the wound environment and influence [...] Read more.
Nanofibrous materials based on chitosan (CS) have attracted considerable attention for advanced wound management due to their excellent biocompatibility and their suitability as drug delivery systems for wound healing applications. Additional surface modification may improve their interaction with the wound environment and influence tissue repair mechanisms. TMC/CS nanofibers were fabricated via electrospinning and subsequently processed into three formulations: unloaded fibers (NCC), norfloxacin-loaded fibers (NCX), and norfloxacin-loaded fibers modified with 2-formylphenylboronic acid (NCXA). The resulting materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and UV–Vis spectroscopy. Their therapeutic performance was evaluated in a standardized deep dermal burn model in Wistar rats, with Vaseline gauze and silver sulfadiazine serving as reference treatments. Wound healing progression was assessed through macroscopic examination, histopathological analysis, immunohistochemical evaluation of TNF-α, IL-1β, IL-17, VEGF, VCAM, and CD163 expression, and systemic IL-8 determination. Physicochemical characterization confirmed homogeneous nanofiber formation, efficient incorporation of norfloxacin, and successful surface modification. All electrospun formulations promoted improved healing outcomes compared with the untreated control group. Among them, the norfloxacin-loaded nanofiber formulation demonstrated the most pronounced wound-healing effect, characterized by faster re-epithelialization, attenuation of inflammatory mediators during later healing stages, and superior tissue architecture restoration. Conversely, the 2-formylphenylboronic acid-modified norfloxacin-loaded fiber formulation maintained a more persistent inflammatory state and exhibited a slower transition into the remodeling phase. Trimethyl chitosan-based nanofibers loaded with norfloxacin show strong potential as multifunctional wound dressing platforms capable of controlled drug release. The findings indicate that formulation composition plays a critical role in regulating inflammation and tissue regeneration, underscoring the need for continued refinement of chitosan-derived nanosystems for burn wound therapy. Full article
(This article belongs to the Section Polymer Fibers)
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19 pages, 5420 KB  
Review
Usnic Acid and Its Topical Use—A Concise Review
by Gabriela Siedlarczyk, Irma Podolak and Agnieszka Galanty
Molecules 2026, 31(12), 2183; https://doi.org/10.3390/molecules31122183 - 22 Jun 2026
Viewed by 548
Abstract
Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA [...] Read more.
Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article
(This article belongs to the Special Issue Chemistry and Biological Activities of Lichens and Fungi)
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20 pages, 3218 KB  
Article
Redox-Responsive GHK-Conjugated Sponge Spicules for Sustained Dermal Delivery and Enhanced Collagen Synthesis
by Won-Kyu Hong, Patrick Po-Han Huang, Diane Duncan, Rocha Marco, Ho-Sung Choi and Young-Wook Jo
Micromachines 2026, 17(6), 750; https://doi.org/10.3390/mi17060750 - 21 Jun 2026
Viewed by 1252
Abstract
Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is [...] Read more.
Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm2 of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm2), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration. Full article
(This article belongs to the Section B5: Drug Delivery System)
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61 pages, 1901 KB  
Review
Transferosomes as Drug Delivery Systems: Design Principles, Deformability, and Translational Challenges
by Enrique A. Nieves, María C. Cotto and Francisco Márquez
Pharmaceuticals 2026, 19(6), 956; https://doi.org/10.3390/ph19060956 - 19 Jun 2026
Cited by 2 | Viewed by 749
Abstract
Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. [...] Read more.
Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article
(This article belongs to the Section Pharmaceutical Technology)
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24 pages, 37298 KB  
Article
Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study
by Hyojin Roh, Young In Lee, Jinyoung Jung, Ngoc Ha Nguyen, Jewan Kaiser Hwang and Jihee Kim
Int. J. Mol. Sci. 2026, 27(12), 5162; https://doi.org/10.3390/ijms27125162 - 6 Jun 2026
Viewed by 1117
Abstract
Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling [...] Read more.
Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling (RF-CWC) designed to optimize thermal distribution and enhance patient tolerance. In a prospective, single-arm clinical trial involving 22 female participants, a single RF-CWC treatment utilizing region-specific static and sliding delivery modes yielded statistically significant improvements in jawline lifting, alongside a volumetric increase in the midface and a concomitant volumetric reduction in the lower face (p < 0.001) over an 8-week follow-up period, with no adverse events reported. To elucidate the underlying cellular mechanisms, the system was further evaluated using an ultraviolet B (UVB)-induced ex vivo human skin model and an in vivo porcine model. Histological, immunohistochemical, and ELISA analyses revealed that RF-CWC effectively mitigated UVB-induced dermal degradation ex vivo by significantly up-regulating elastin, insulin-like growth factor, and hyaluronic acid, while down-regulating matrix metalloproteinase-1, interleukin-1α, and heat shock protein 72 (p < 0.05). Furthermore, the in vivo model demonstrated time-dependent increases in collagen types I and III and elastin without thermal tissue damage, with the sliding mode and higher shot counts correlating with enhanced extracellular matrix (ECM) remodeling. Comparative analyses demonstrated that RF-CWC achieved superior ECM restoration and reduced inflammatory cell infiltration relative to traditional cryogen spray-cooled RF systems. Taken together, these findings suggest that the RF-CWC system may promote robust ECM remodeling and significant facial neocollagenesis while minimizing inflammatory responses, potentially presenting an optimized, highly effective, and patient-friendly advancement in MRF technology. Full article
(This article belongs to the Special Issue Skin Extracellular Matrix and Basement Membrane)
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33 pages, 21681 KB  
Article
Silibinin-Loaded Proniosomal Gel for Cutaneous Application: Pharmaco-Technical Characterization and In Vitro–In Ovo Biocompatibility
by Andreea Smeu, Ioana Olariu, Iasmina Marcovici, Diana Haj-Ali, Lavinia Vlaia, Vicențiu Vlaia, Alina Tănase, Raluca Mioara Cosoroabă, Vlad Socoliuc and Cristina Adriana Dehelean
Gels 2026, 12(6), 504; https://doi.org/10.3390/gels12060504 - 5 Jun 2026
Cited by 1 | Viewed by 764
Abstract
The skin serves as the first line of defense, being highly prone to external damage. Silibinin (SIL) exerts skin-protective properties, but its topical use requires a suitable delivery system. Despite the growing interest in proniosomal platforms loaded with natural products, their application for [...] Read more.
The skin serves as the first line of defense, being highly prone to external damage. Silibinin (SIL) exerts skin-protective properties, but its topical use requires a suitable delivery system. Despite the growing interest in proniosomal platforms loaded with natural products, their application for the cutaneous delivery of SIL remains scarcely explored. This study proposes the pharmaco-technical characterization and preclinical safety evaluation of a SIL-loaded proniosomal gel (SIL-PG) for skin application. SIL-PG was produced using the coacervation phase separation technique, analyzed in terms of physicochemical and technological properties, and evaluated in vitro and in ovo for potential cytotoxic and irritant effects. SIL-PG retained a yellowish, creamy aspect, proper rheological behavior and spreadability, gradual in vitro drug release, sustained permeation, and an adequate safety profile, evidenced by the lack of cytotoxicity in HaCaT keratinocytes and spheroids and the absence of irritant potential in 3D EpiDerm™ reconstructed human tissues and on the chorioallantoic membrane. Overall, these findings emphasize SIL-PG as a potential pharmaceutical formulation for dermal use, with favorable pharmaco-technical characteristics and in vitro–in ovo biocompatibility. Full article
(This article belongs to the Special Issue Functional Gels Loaded with Natural Products (2nd Edition))
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