Search Results (1,097)

Lignin is one of the most abundant natural biopolymers and plays a crucial role in the development of safe and sustainable alternatives for healthcare products. In this study, we employed molecular dynamics simulations and free energy calculations to investigate lignin derivatives’ interactions with skin-like membranes. Specifically, we designed a small lignin derivative composed of syringyl and guaiacyl subunits. Our results reveal that molecular size, concentration, and thermal conditions critically influence the insertion, interaction dynamics, and localization behavior of lignin derivatives. Notably, variations in these parameters induce distinct behaviors, including rapid membrane insertion, hydrogen bonding, clustering, and surface adhesion. The findings provide insights into the molecular mechanisms governing lignin derivatives’ interactions with skin-like membranes, with implications for developing bio-based skincare formulations and transdermal delivery systems. Our results highlight the importance of molecular size and concentration in optimizing lignin-derived compounds for dermatological and therapeutic applications. Full article

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

This study reports the development of electrospun poly(methyl methacrylate) (PMMA) fiber mats incorporating ibuprofen (IBU)-intercalated layered double hydroxides (LDH) for enhanced transdermal drug delivery systems (TDDS). IBU, in its anionic form, was successfully intercalated into LDH, which possesses anion exchange capabilities, and subsequently embedded into PMMA fibers via electrospinning. In vitro drug release experiments demonstrated that UPMMA–LDH–IBU fibers exhibited significantly higher IBU release than PMMA–IBU controls. This enhancement was attributed to the improved hydrophilicity and water absorption imparted by the LDH, as confirmed by contact angle and water uptake measurements. Furthermore, artificial skin permeation tests revealed that the UPMMA–LDH–IBU fibers maintained comparable release rates to those observed during buffer immersion, indicating that the rate-limiting step was the diffusion of IBU within the fiber matrix rather than the interface with the skin or buffer. These findings highlight the critical role of LDH in modulating drug release behavior and suggest that UPMMA–LDH–IBU electrospun fiber mats offer a promising and efficient platform for advanced TDDS applications. Full article

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

Background and objectives: Exercise-induced muscle injury, a consequence of intense physical activity, is characterized by subsequent inflammation. Sports massage frequently employs massage oils, such as jojoba (Simmondsia chinensis (Link.) C.K.Schneid., Simmondsiaceae) oil, which is recognized for its anti-inflammatory properties. Therefore, this study investigated the potential of jojoba oil to alleviate exercise-induced muscle injury. Materials and Methods: Male hairless mice, aged eight weeks, were randomly allocated into one of four groups: a naïve control group, a sedentary group treated with jojoba oil (JO), an exercise group without oil application, and an exercise group treated with jojoba oil (JO + Ex). In the JO and JO + Ex groups, 4 μL of jojoba oil per gram of body weight was applied topically to the dorsal skin of the mice 30 min prior to treadmill exercise. Subsequently, plasma biochemical parameters, gene expression in various tissues, and plasma cytokine levels were evaluated. Results: Topical application of jojoba oil did not significantly impact plasma cytokine concentrations. However, it significantly decreased the expression levels of pro-inflammatory cytokines (Il-1b and Il-6 in the soleus muscle; Il-1b in the gastrocnemius muscle). Conclusions: Our findings suggest that sports massage with jojoba oil may aid in reducing exercise-induced muscle injury and inflammation. Full article

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

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

Introduction: Chronic low-back pain (CLBP) is a leading cause of disability, often requiring opioid therapy when conservative treatments fail. Transdermal buprenorphine and oral oxycodone/naloxone are commonly used, but their comparative effectiveness and safety remain underexplored. Materials and Methods: In this retrospective cohort study, 173 patients with CLBP treated at our center between June 2022 and May 2024 were analyzed. Group A (n = 88) received transdermal buprenorphine (5–15 μg/h), while Group B (n = 85) was treated with oral oxycodone/naloxone (10/5–20/10 mg/day). Treatment lasted four weeks, with dose titration after one week if pain was uncontrolled. Pain intensity (VAS), functional status (ODI), rescue medication use, and adverse effects were assessed at baseline and during follow-up. Results: Both groups showed significant reductions in VAS and ODI scores. Buprenorphine led to a greater functional improvement (ODI reduction p = 0.04) and a trend toward greater pain reduction (VAS p = 0.08). Rescue drug use was significantly lower in Group A (53.4%) compared to Group B (78.8%, p = 0.003). Adverse events were more frequent in the oxycodone group, particularly nausea and constipation. Conclusions: Transdermal buprenorphine provided comparable or superior analgesia with better tolerability and reduced reliance on rescue medication. It represents a safer, effective alternative for CLBP management in routine clinical practice. Full article

Androgenetic alopecia (AGA), the most common form of hair loss, imposes considerable psychosocial and medical burdens. Current topical treatments are limited by suboptimal efficacy, slow onset, side effects, and poor patient adherence. Although numerous reviews have explored natural plant-based strategies for managing AGA, most offer fragmented evidence with limited systematic correlation between mechanistic studies and clinical outcomes concerning single plant constituents. This review critically synthesizes recent pharmaceutical advances in AGA therapy, with a focus on the synergistic potential of multifunctional plant extracts integrated with nanotechnology enhanced cutaneous delivery systems. We begin by examining the mechanistic basis of AGA pathogenesis and the limitations of existing treatments to identify unmet therapeutic needs. Next, we systematically evaluate plant extracts supported by robust in vitro, in vivo, and clinical evidence for their anti-androgenic, anti-inflammatory, antioxidative, and anti-apoptotic properties. Finally, we address key biopharmaceutical challenges in transdermal delivery for AGA and discuss how nanocarriers can overcome these barriers to improve local drug bioavailability and target specificity. By bridging phytochemistry and nanomedicine, this review provides novel insights and a pharmaceutics-oriented framework aimed at developing safer, more effective, and patient-compliant topical therapies for AGA. Full article

Nanoparticle-based transdermal drug delivery systems (TDDS) have emerged as a revolutionary approach for antiparasitic therapy, addressing key challenges such as poor bioavailability, systemic toxicity, and drug resistance. This review highlights the advancements in nanotechnology-driven TDDS for combating zoonotic parasitic diseases, including leishmaniasis, malaria, and infections treated by broad-spectrum drugs like ivermectin and albendazole. By leveraging nanocarriers such as liposomes, nanoemulsions, and microneedles, which enhance skin permeation, enable controlled drug release, and improve targeting specificity. For instance, deformable transfersomes and ethosomes achieve high transdermal efficiency without chemical adjuvants, while microneedle arrays physically bypass the stratum corneum for precise delivery. Furthermore, sustained-release hydrogels and stimuli-responsive nanoparticles optimize therapeutic efficacy and reduce adverse effects. Despite promising results, clinical translation faces challenges in manufacturing scalability, long-term safety, and accessibility in resource-limited settings. Future directions include bioinspired nanocarriers, artificial intelligence (AI)-driven design, and integration with global health initiatives like “One Health”, all aimed at ensuring equitable implementation. This review highlights the transformative potential of nanotechnology in achieving sustainable antiparasitic solutions for zoonotic diseases. Full article

Background/Objectives: Transdermal bicarbonate (TBC) or carnosine (TC) have been sold as a convenient ergogenic aid, though little evidence supports these claims. The purpose of this study was to investigate if TBC or TC would improve high-intensity endurance cycling. Methods: Data were collected remotely using Zwift online platform. Fifteen cyclists completed four trials comprising five 9.1 km laps: warm-up lap, three interval laps (3 × 900 m hills, and 3 × 300 m sprints), and a 9.1 km time trial (TT) lap. A familiarization (FAM) trial followed by three randomized trials using a TBC, TC, or placebo (PLAC) lotion were completed. Trial data were assessed using general linear models to compare differences between conditions across cycling trials (p < 0.05). Results: Mean ± SD. 60 min mean max power (MMP60) was 2.9 ± 0.9 W/kg and ranged from 1.3 to 4.1 W/kg for participants. Exercise trials were 89.8 ± 17.0 min long. Laps 2–4 were ridden at 86.4 ± 7.3% and hill climbs at 131.6 ± 21.1% of MMP60, while sprints averaged 83.2 ± 17.7% of 30 s mean max power (MMP30s) and the TT ridden at 95.4 ± 8.7% of 20 min mean max power (MMP20). FAM trials were significantly lower (p < 0.05) in all power output measures, except TC sprints, and no heart rate or rating of perceived exertion differences. Similarly, there were no statistical differences in performance between any condition trials or placebo trial, but TBC hill climb power was significantly higher (p = 0.038) than TC trials. Conclusions: There are no apparent ergogenic benefits from TBC or TC during high intensity cycling performance. Full article

Background: Skin whitening agents often face challenges such as poor stability and low permeability. To overcome these issues, a novel 4-butylresorcinol (4-BR)/D-a- Tocopherol Polyethylene Glycol Succinate (TPGS) deep eutectic solvent (DES) system was developed, which can self-assemble into carrier-free nanoparticles (NPs). Methods: The 4-BR/TPGS DES was synthesized and characterized by theoretical calculations, DSC, FTIR, 1H-NMR, and 2D NMR to confirm its successful formation. Results: The self-assembled 4-BR/TPGS DES NPs showed a 3.46-fold increase in skin permeability, a 1.53-fold improvement in 4-BR stability, a 1.55-fold increase in melanin inhibition in B16 cells, and a 2.16-fold higher melanin suppression in zebrafish compared with traditional 4-BR oil-based formulations. These results indicated the excellent whitening efficacy and transdermal delivery potential of this formulation. Conclusions: The combination of TPGS-based DES and self-assembly technology represents a revolutionary approach for advanced transdermal delivery and the development of skin care products. Full article

Purpose: This study was designed to develop a nanoparticle-based methotrexate (MTX) and sorafenib (SRF)-loaded transferosome (MTX-SRF-TFS) for effective management of arthritis through the transdermal route. Methods: For the preparation of MTX-SRF-TFS, the thin-film hydration technique was selected and optimized using Box–Behnken Design. The particle size of the nanoparticles was determined using a Malvern Zeta sizer and electron microscopy. An in vivo skin retention and penetration study was also conducted to evaluate the designed delivery system. Furthermore, the therapeutic response of MTX-SRF-TFS was determined using the CFA-induced mouse model. Results: The optimized MTX-SRF-TFS formulation (F4), having an average particle size (PS) of 162.20 ± 2.89 nm and percent entrapment efficiency (%EE) of MTX and SRF of 92.16 ± 4.95 and 81.54 ± 3.23, respectively, was selected for further assessment. Due to the deformable nature of MTX-SRF-TFS, MTX and SRF penetrate more deeply into the cutaneous layers, exhibiting an enhanced transdermal effect, as shown by the results of ex vivo skin permeation and retention studies. Furthermore, in vivo anti-arthritic studies have shown the superior pharmacodynamic response of MTX and SRF when incorporated into transferosomes, as it caused a marked reduction in arthritic score and paw diameter in CFA-induced arthritis in BALB/c mice. Histopathology analysis and X-ray radiography also confirmed the findings that MTX-SRF-TFS has improved anti-arthritic response in contrast to plain MTX-SRF gel. Conclusions: The MTX-SRF-TFS is highly effective in managing CFA-induced arthritis, and the designed delivery system should be further evaluated on pharmacokinetic grounds to progress towards clinical studies. Full article

Background: Psoriasis is a chronic inflammatory skin disorder for which topical medications are the preferred treatment option. However, current therapies are limited by adverse reactions, drug resistance, and economic burdens. Dictamni Cortex (DC; the root bark of Dictamnus dasycarpus Turcz.) has a long history in the treatment of psoriasis, with its transdermal bioactive constituents serving as the pharmacodynamic foundation for topical anti-psoriatic therapy. Methods: Building on the separation of DC’s chemical constituents, this study integrated ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and network pharmacology, along with activity verification, to investigate the anti-psoriatic active components among the transdermal constituents of DC. Results: Forty-one chemical constituents were characterized in DC, including 26 transdermally permeable compounds, predominantly alkaloids and limonoids. Network pharmacological analysis revealed core targets, including MMP9 and TLR4, as well as multiple pathways related to inflammatory and immune responses. Molecular docking studies identified dictamnine, jangomolide, rutaevin, and other key transdermal constituents that exhibited high binding affinity to core targets. In vitro validation showed that these compounds significantly suppressed cellular proliferation (p < 0.05) and downregulated Ki67 mRNA expression (p < 0.05) in the psoriasis-like HaCaT cell model. Concurrently, they significantly reduced secretion of key pro-inflammatory cytokines, including IL-17A, IL-22, IL-1β, IL-6, and IL-8 (p < 0.05). Comprehensive comparative analyses confirmed that dictamnine exhibited ideal anti-psoriatic efficacy. Conclusions: These results provide a pharmacological substance basis for the development of external preparations of DC for treating psoriasis and provide novel research concepts for investigating the pharmacodynamic material basis of Traditional Chinese Medicine topical drugs. Full article

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