Search Results (1,041)

Biomimetic structures are now a major topic of research, as natural systems achieve high performance through hierarchical organization, multifunctional interfaces, and scale-bridging design principles. Nanofabrication provides a powerful approach to recapitulate biological architectures from the nanoscale to the macroscale, allowing accurate control of the surface chemistry, geometry, transport, mechanics and function. Recent work demonstrates that this approach is especially critical for bionic devices and systems, including biosensors, drug delivery platforms, tissue-engineered constructs, organ-on-chip systems, soft robots, and biohybrid devices. The aim of this review is to provide a systematic overview on how nanofabrication allows the construction of biomimetic structures, with emphasis on bio-templating and replication of natural structures, applications of nanofabrication in bionic devices and systems, and cross-scale biomimetics. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs), including naproxen, are widely used for the treatment of pain and inflammation; however, their therapeutic application is limited by poor aqueous solubility and low bioavailability. This study aimed to synthesize and characterize a novel amino acid-based naproxen derivative, L-phenylalanine menthol ester naproxenate ([PheOMent][NAP]), develop liposomal formulations containing the obtained compound, and evaluate their physicochemical properties and transdermal delivery potential. The derivative was synthesized via a three-step procedure and characterized using NMR, FT-IR, TG, DSC, and XRD analyses. Compared with naproxen, [PheOMent][NAP] exhibited lower lipophilicity (log P = 1.36 vs. 1.70). Liposomal formulations containing the modified derivative showed high encapsulation efficiency (89.6–90.7%), higher than that observed for naproxen-loaded liposomes (51.7–54.7%). The prepared systems exhibited bimodal particle size distributions, comprising both submicrometre and micrometre vesicle populations depending on the preparation method, as well as negative zeta potential values (−18.17 to −23.72 mV) and pH values ranging from 6.18 to 7.07, demonstrating physicochemical characteristics suitable for topical formulations. In vitro permeation studies using porcine skin demonstrated markedly enhanced transdermal delivery of [PheOMent][NAP]. After 24 h, cumulative permeation exceeded that of naproxen formulations by more than 1.5-fold (416.7 vs. 281.6 μg cm⁻²). These findings indicate that liposomal formulations containing amino acid-modified naproxen derivatives represent a promising strategy for improving transdermal NSAID delivery. Full article

Eye drops remain the principal topical treatment for ocular infections, yet rapid precorneal clearance, variable dose delivery and limited tissue penetration can restrict local drug availability and necessitate frequent administration. Conjunctival inserts have long been investigated as a means of extending ocular residence and thin film inserts offer a more adaptable solid dosage form that may provide a defined drug-containing unit, prolonged local exposure and hydration-dependent dissolution or transformation within the conjunctival sac. Clinical translation remains limited by substantial variability in formulation design, manufacturing control and performance testing. This review critically evaluates the manufacture and characterisation of ocular anti-infective thin film inserts, with the aim of identifying the principal factors that determine reproducibility, interpretability and progression beyond formulation feasibility. Film architecture, polymer selection and drug-loading strategy are considered in relation to the physicochemical characteristics of the active pharmaceutical ingredient and the intended behaviour of the finished insert. Solvent casting remains the most extensively investigated manufacturing approach, while extrusion, electrospinning and additive manufacturing broaden the available processing options. Across these methods, incomplete specification of material and process variables frequently restricts comparison and reproducibility. Testing procedures are similarly heterogeneous and often assess individual attributes without establishing how the finished insert performs under conditions relevant to conjunctival administration. Particular limitations concern dosage-unit uniformity, hydration and matrix transformation, drug-release models and the interpretation of antimicrobial activity. Progression towards clinically relevant products will require indication-led development in which manufacturing control, pharmaceutical quality, ocular compatibility and biorelevant performance evaluation are considered as connected elements. This approach may provide a stronger basis for determining whether the potential advantages of ocular anti-infective thin film inserts can be translated into reproducible and clinically useful dosage forms. Full article

Breast cancer is among the most common cancers globally. While several advancements have been made to improve breast cancer management, there is still a need to find innovative ways to deliver drug therapy to improve efficacy and side effects associated with treatment. Among these methods, local and targeted drug delivery is particularly promising. The current review highlights localized polymer-based methods to effectively deliver breast cancer therapy, with a specific focus on the strengths and limitations of these systems. Injectable and surgically implanted scaffolds, microneedles, topical patches, liquid and semisolid topical drug carriers are amongst some of the delivery systems discussed. Highlighted in the discussion is how physiological changes that occur during breast cancer should be considered and utilized when developing drug formulations, by specifically exploiting the tumor microenvironment. Remaining gaps and future areas for drug delivery research are highlighted including personalized medicine and insights into novel drug delivery systems like nanomedicines and three-dimensional drug printing. Full article

Background/Objectives: The pharmacological management of inflammation remains a clinical challenge, driving the demand for advanced topical formulations. This study utilizes a “smart-NADES” (natural deep eutectic solvent) paradigm to develop an innovative anti-inflammatory topical system. The aim was to evaluate the integrated antioxidant potential, alongside the in vitro and in vivo anti-inflammatory activities, of a novel smart-NADES licorice root extract and its hydrogel formulation. Methods: A NADES system composed of D-sorbitol and L-lactic acid (3:1) was employed for licorice root extraction. The antioxidant capacity was assessed using three independent assays and integrated via the Relative Antioxidant Capacity Index (RACI), while phytochemical interactions were quantified using the Chou–Talalai Combination Index (CI). In vitro anti-inflammatory activity was evaluated via protein stabilization capacity, and in vivo efficacy was validated using a formalin-induced paw edema model in mice. Results: The NADES extract contained glycyrrhizic acid levels of 6.3 ± 0.3 mg/g and showed strong antioxidant synergism in the DPPH assay (CI = 0.49 ± 0.07). The extract exhibited potent total antioxidant capacity (IC₅₀ = 11.9 ± 0.6 μg/mL) with a superior RACI score (1.23). In vitro protein stabilization (IC₅₀ = 63 ± 5 μg/mL) was comparable to diclofenac sodium. The 5% hydrogel numerically surpassed the commercial 2% diclofenac Emulgel (67.5% vs. 32.9% inhibition, respectively) at 24 h, although the direct pairwise comparison did not reach statistical significance (p = 0.186). Conclusions: The developed smart-NADES licorice hydrogel represents an effective, green formulation with pronounced topical anti-inflammatory properties, establishing a robust pharmacological rationale for advanced topical drug delivery. Full article

Mitochondria are increasingly recognized as integrated bioenergetic and signaling hubs across disease contexts, but the rapidly expanding literature remains fragmented across mechanisms, diseases, and analytical vocabularies. This study mapped the disease-oriented literature on mitochondrial bioenergetics and signaling from 2014 to 2025 using a mechanism-centered text-mining framework integrating dictionary-based annotation and topic modeling. Records retrieved from Web of Science, Scopus, and PubMed were harmonized into a final corpus of 166,462 title–abstract records. Dictionary-based annotation was used to identify disease and mitochondrial mechanism signals, followed by disease–mechanism co-occurrence, lift-based enrichment, exploratory drug/compound annotation, non-negative matrix factorization (NMF), and structural topic modeling (STM). Publication output increased approximately 2.6-fold over the study period. The literature was organized around a central mechanistic backbone involving ROS/redox biology, cell death pathways, bioenergetics/OXPHOS, mitochondrial dysfunction/homeostasis, and quality-control processes. Cancer, cardiometabolic/metabolic disease, and neurodegeneration/neurological injury were the dominant disease contexts. Enrichment analysis revealed disease-characteristic mitochondrial signatures, while NMF identified a 20-topic thematic structure and STM showed increasing emphasis on mitochondrial dysfunction, immune-inflammatory signaling, omics-based prognostic signatures, therapeutic delivery systems, and cancer progression/resistance. Overall, mitochondrial disease research is shifting toward an integrated, application-oriented framework in which mitochondria are positioned as bioenergetic, signaling, immune-regulatory, and therapeutic-response hubs. Full article

Chronic wounds remain a significant clinical challenge due to persistent inflammation and impaired tissue repair. Anti-inflammatory agents play a pivotal role in wound management by reducing excessive inflammation, preventing further tissue damage, and creating a microenvironment conducive to healing. Among them, Ketoprofen, a non-steroidal anti-inflammatory drug, is effective in modulating inflammation. However, its systemic administration is associated with adverse effects, highlighting the need for localized and controlled delivery systems. Gelatin-based carriers provide important advantages, including biocompatibility, biodegradability, low immunogenicity, cost-effectiveness, and the ease of chemical modification to tailor drug release profiles. In this pioneering study, gelatin-based microspheres crosslinked with tannic acid were developed to achieve sustained topical release of Ketoprofen. The microparticle system was produced through the single water-in-oil emulsification process and optimized by varying homogenization speed, crosslinking time, and molar ratio. Morphological, physicochemical, functional, and biological characterizations were conducted. The optimized formulation yielded spherical microspheres (5–35 µm) with high crosslinking efficiency and a controlled drug release profile over time. COX inhibition assays provided preliminary evidence that released Ketoprofen-retained inhibitory activity under the assay conditions, while cytocompatibility tests supported the short-term compatibility of the system within the tested concentration range. A qualitative wound-model test provided preliminary evidence of powder hydration, film formation, and macroscopic retention. Overall, tannic acid-crosslinked gelatin microspheres represent a biocompatible and promising platform for localized drug delivery of non-steroidal anti-inflammatory in wound management. Full article

Objectives: The present study was designed to repurpose aripiprazole (AR) as an antifungal drug for the management of topical candidiasis using a bioadhesive sponge incorporating a hyaluronic acid (HA)-, ceramide-, and terpene-based vesicular nanosystem (HCT-NS). Methods: AR-loaded HCT-NS were formulated by the modified ethanol injection method with varying amounts of HA, ceramide, and two types of terpenes. The formulation optimization of AR-loaded HCT-NS was carried out by a full factorial design. The responses evaluated were zeta potential (ZP), particle size (PS), and entrapment efficiency (EE). Results: The optimized AR-loaded HCT-NS has 5 mg of HA, 10 mg of ceramide, and fenchone, which showed spherical vesicles with EE of 81.21 ± 0.01%, PS of 223.25 ± 11.25 nm, polydispersity index (PDI) of 0.492 ± 0.003, and ZP of −27.74 ± 0.04 mV. The optimum HCT-NS showed a greater drug release in comparison to the AR suspension. In addition, the selected HCT-NS exhibited good bioadhesive characteristics and stayed stable during storage. Confocal laser scanning microscopy confirmed the penetration of the fluorescently optimized HCT-NS via the skin. Further, the scanning electron microscope image indicates the porous structure of the formed sponge. In vivo evaluations for the optimum HCT-NS sponge showed a good antifungal impact against Candida albicans. The safety of topical treatment was confirmed by histopathological examination. Conclusions: Taken together, the results here suggest that the AR-loaded HCT-NS sponge showed potent antifungal activity against Candida albicans fungal infection. Full article

Background/Objectives: Breast cancer remains one of the most prevalent malignancies worldwide, highlighting the need for safer and more effective therapeutic strategies. Curcumin has shown considerable anticancer potential; however, its clinical application is limited by poor aqueous solubility and low skin permeability. Methods: Therefore, a curcumin-loaded microemulsion (CUR-ME) was developed and optimized using a Box–Behnken design, followed by incorporation into a Carbopol 934 gel for topical breast cancer therapy. Results: The optimized formulation exhibited a particle size of 177.4 nm, a polydispersity index of 0.1309, and a zeta potential of −4.45 mV, indicating favorable physicochemical characteristics. CUR-ME demonstrated superior dose-dependent cytotoxicity against MCF-7 breast cancer cells, with a lower IC₅₀ 8.89 µg/mL than free curcumin IC₅₀ 9.83 µg/mL. Furthermore, Hoechst 33342 staining and the DCFDA assay confirmed enhanced apoptosis and intracellular reactive oxygen species generation in CUR-ME-treated cells, indicating improved cellular uptake and anticancer activity. Rheological and texture profile analyses demonstrated suitable viscosity, firmness, and spreadability for topical application. In vitro drug release revealed sustained release from the CUR-ME gel, achieved through the polymeric gel matrix, which increased viscosity, entrapped microemulsion droplets, and acted as a diffusion barrier to prolong drug retention and release. Confocal laser scanning microscopy further confirmed enhanced skin penetration of CUR-ME. Conclusions: Collectively, these findings demonstrate that the developed CUR-ME gel is a promising topical drug delivery system with sustained release, improved skin retention, and enhanced therapeutic potential for breast cancer management. Full article

Mucosa can be found in the eyes, oral cavity, bladder, vagina, airways, and gastrointestinal tract. It is an attractive route of administration for systemic or topical delivery of therapeutics. However, the mucus layer acts as a protective barrier, limiting the amount of biomolecules that reach the underlying epithelium. Mucoadhesion, mucodiffusion, and mucolysis are well-established mucointeractive strategies that can improve therapeutic outcomes, but due to their individual limitations, the resulting delivery is often still unsatisfactory. In recent years, drug delivery systems have emerged that combine multiple mucointeractive strategies, which we define here as hybrid mucointeractive delivery systems. This work aims to provide a general overview of such drug delivery systems, which include particle-releasing macrostructures such as gels, foams, films, and fibers, as well as systems such as zeta potential-changing particles and self-emulsifying drug delivery systems. Their potential, possible future, and limitations are discussed as well. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

Transdermal drug delivery offers several advantages over conventional routes. However, its use is limited by the low permeability of the stratum corneum. This limitation is especially significant in the case of hydrophilic drugs such as caffeine. This study explored microemulsion systems to enhance the transdermal delivery of caffeine (CF) using chemical penetration enhancers as cosurfactants. Kolliphor^® PS80 (PS80), Kolliphor^® RH40 (RH40), Kolliphor^® PS20 (PS20), and Kollicream^® OD (OD) were evaluated as cosurfactants for the first time in microemulsion formulations consisting of water, oil, and a fixed surfactant-to-cosurfactant ratio of 4:1 (w/w), with 14% of each cosurfactant incorporated. CF skin permeation from microemulsions was assessed via in vitro permeation studies using Franz diffusion cells and human cadaver skin. The results showed that OD-based microemulsions achieved approximately 3-fold higher CF skin permeation compared with the control formulation and 1.4–1.6-fold higher permeation compared with formulations containing PS80, RH40, and PS20. Furthermore, CF solubility in the four cosurfactants followed the order: PS20 > RH40 > PS80 > OD. These findings indicate that PS20 provides the highest solubility for CF among the tested cosurfactants. The results also included visual evaluations. No significant changes in appearance or physical properties were observed during the 10-month study. All samples remained clear and stable throughout the testing period. This study uniquely highlights the critical role of cosurfactant selection in optimizing microemulsion-based transdermal delivery systems. This work addresses a previously unexplored aspect, namely, the effect of cosurfactants with different physicochemical properties on the skin permeation of caffeine. The findings provide valuable insight into developing more effective transdermal and topical drug delivery systems. Full article

Cyclodextrins are cyclic carbohydrates capable of forming inclusion complexes with a wide range of molecules, thereby improving their solubility, stability, and bioavailability. Traditionally, cyclodextrins have been extensively applied in the food industry owing to their functionality and safety profile. However, their use in cosmeceuticals, a rapidly growing area that lies between cosmetics and pharmaceuticals, remains relatively underexplored. Given the increasing demand for scientifically validated, high-performance skincare formulations, cyclodextrins are emerging as promising compounds that can address several formulation challenges. The principal question is whether cyclodextrins represent a worthwhile investment for the future of cosmeceutical innovation. This article aims to provide a comprehensive, evidence-based overview of the current and potential roles of cyclodextrins as safe, effective, and multifunctional carriers in advanced skincare science. The current state of research on the application of cyclodextrins in cosmeceutical formulations is evaluated, with particular focus on active ingredients commonly used in dermatological care, such as vitamins A and C, coenzyme Q10, kojic acid, arbutin, and UV filters. For each of these compounds, relevant in vitro, in vivo, and clinical studies are reviewed in order to assess how cyclodextrin complexation influences key parameters, including solubility, stability, controlled release, skin penetration, and the reduction in adverse reactions. In addition, the use of cyclodextrins in the treatment of dermatological conditions such as acne, psoriasis, and rosacea is examined, highlighting their potential value, particularly in combination with azelaic acid and salicylic acid, well-known agents used to manage these conditions. Beyond their advantages, the limitations and challenges that currently restrict broader implementation of cyclodextrins in cosmeceuticals are also discussed, including cost variability, solubility constraints with certain substances, formulation incompatibilities, and regulatory considerations. Future perspectives are explored, particularly the development of novel modified and amphiphilic cyclodextrins, as well as their integration into nanotechnology-based systems and into intelligent, personalized skincare. Full article

Cutaneous leishmaniosis (CL) remains a major neglected tropical disease, with current therapies constrained by toxicity, high cost, and variable efficacy. Here, we evaluated an immunochemotherapy strategy combining topical amphotericin B (AmB) with the therapeutic DNA vaccine HisAK70 in a murine model of Leishmania major infection. BALB/c mice were subcutaneously infected and treated with topical AmB cream alone, AmB plus HisAK70, or paromomycin (PM) as a reference therapy. Therapeutic efficacy was assessed through lesion progression, parasite burden in draining lymph nodes and spleen, and immunological markers associated with parasite control. Both PM and the combined AmB + HisAK70 treatment significantly reduced lesion progression and markedly decreased parasite burden compared with infected controls, demonstrating effective control of local infection and systemic dissemination. Importantly, the combination therapy enhanced the efficacy of AmB alone, supporting the beneficial contribution of vaccine-driven immune modulation to therapeutic outcome. Therapeutic efficacy was associated with reduced arginase activity in infected tissues and an increased IFN-γ/IL-4 ratio, indicative of a protective Th1-oriented immune response. Together, these findings highlight immunochemotherapy as a promising strategy for CL treatment, integrating localized topical drug delivery with targeted immune activation to improve therapeutic efficacy while potentially reducing systemic toxicity. Full article