Search Results (372)

Background: Additive manufacturing provides a rapid and flexible alternative to conventional micromolding for producing microneedle systems. This study evaluates the potential of a cost-effective LCD 3D printer for fabricating microneedle arrays (MNAs) and investigates how the geometry of MNAs and the formulation of hydrogel influence the performance of lidocaine-coated arrays. Methods: Conical and pyramidal MNAs, along with a reservoir plate, were designed and manufactured. Lidocaine-loaded and placebo hydrogels with two different polymer concentrations were prepared for dip-coating using both single and multilayer applications. Mechanical resistance and insertion efficiency were evaluated under controlled compression. The physicochemical behavior of the hydrogels were characterized, including pH, spreadability, adhesiveness, and rheological behavior. The uniformity of the coating was analyzed using 3D confocal microscopy. Drug loading was quantified by HPLC, drug release was studied using Franz diffusion cells, and skin penetration was confirmed by 3D confocal imaging and Raman mapping. Results: Conical microneedles exhibited high mechanical integrity, showing only a 2% reduction in height compared to 4% for pyramidal MNAs. Stronger drug signals were achieved in deeper skin layers with the conical geometry, indicating enhanced penetration, while pyramidal MNAs provided slightly higher lidocaine loading due to their larger lateral surface. Hydrogels with higher polymer content produced more stable, uniform coatings, particularly when applied in three layers. Rapid drug release was observed, with over 70% of the drug delivered within minutes. Conclusions: LCD 3D printing offers a cost-effective approach for fabricating MNAs with suitable structural stability and sharpness. The optimized hydrogel formulation ensured uniform coverage, as well as maximal and consistence penetration, making this platform a promising candidate for the dermal delivery of other potent drugs. Full article

Background: Total glycosides of peony (TGP) have therapeutic potential for immune-related and inflammatory skin diseases, but their skin absorption is not satisfactory. This study aims to investigate how Evodia rutaecarpa volatile oil (VO-ER) enhances the permeability of TGP. Methods: Safety assessment was conducted through cell delivery and skin erythema tests. The chemical composition of VO-ER was identified via GC-MS. The study was conducted using modified Franz diffusion cells, microdialysis, confocal laser scanning microscopy (CLSM), attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), molecular docking and molecular dynamics simulations (MD), laser Doppler flowmetry (LDF), and the western blotting method. Results: The study found that VO-ER promotes the permeation of total glycosides of peony in a concentration-dependent manner by disrupting the intercellular lipid tissue structure, downregulating the expression of claudin-1, claudin-7, and occludin, and improving local microcirculation, thereby promoting the absorption of TGP. Conclusions: VO-ER enhances the transdermal absorption of TGP through multiple mechanisms, such as disrupting the skin lipid barrier, downregulating tight junction proteins, and improving local skin microcirculation. This study provides a theoretical basis for VO-ER as a safe and effective new transdermal penetration enhancer, offering support for the development of topical preparations containing Evodia rutaecarpa and Paeonia lactiflora. Full article

Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This study aimed to quantitatively evaluate the ex vivo buccal permeation of angiotensin II (Ang II), used as a hydrophilic peptide model, when associated with NLCs compared with free peptide under matched Franz diffusion cell conditions. Methods: Ang II-associated NLCs were prepared by melt emulsification combined with a low-energy injection technique. Particle size, polydispersity index, and zeta potential were determined by dynamic light scattering and laser Doppler electrophoresis. Association efficiency and drug loading were quantified by indirect spectrofluorometric analysis. Ex vivo permeation studies were conducted using porcine buccal mucosa mounted in Franz diffusion cells, and cumulative permeation, steady-state flux, and apparent permeability coefficients were calculated. Results: The NLCs exhibited nanometric size, moderate polydispersity, and association efficiency above 80%, and remained colloidally stable at 4 °C for 28 days. In ex vivo experiments, Ang II-associated NLCs showed measurable cumulative permeation, reaching approximately 9% after 2 h, whereas free Ang II was not detected in the receptor compartment under the tested conditions. Conclusions: This work provides a quantitative ex vivo buccal transport comparison of a hydrophilic peptide model delivered as NLC-associated versus free peptide under matched Franz cell conditions. The findings support further investigation of NLC-based approaches for buccal delivery of vasoactive peptides and provide a rational basis for future in vivo evaluation of mucosal delivery performance and systemic exposure. Full article

Background: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) represents an emerging challenge in veterinary dermatology. Commercially available ozonated oils promise antibacterial activity, but their efficacy under physiologically relevant conditions remains unexplored. Objective: We aimed to evaluate the efficacy of commercial ozonated olive oil product (800 mEq O₂/kg) against MRSP using an established in vitro model and a newly presented ex vivo canine skin model. Materials and Methods: In vitro susceptibility testing determined minimum inhibitory concentrations (MIC) and time–kill kinetics. Subsequently, canine skin samples were mounted in Franz diffusion cells, inoculated with MRSP (~10⁶ colony-forming units [CFU]), and treated for 8 h with ozonated or placebo olive oil. Bacterial viability was assessed by quantitative culture and histopathology. Results: In vitro testing demonstrated antibacterial activity for ozonated oil (MIC < 20% v/v) compared to placebo oil (90% v/v), with ozonation-specific bactericidal effects. However, ex vivo testing showed no MRSP reduction for either oil versus untreated controls, with bacterial localization in superficial dermis unchanged. Conclusions: Despite in vitro activity, this ozonated olive oil failed to reduce MRSP in ex vivo skin, revealing that tissue barriers prevent antibacterial delivery. These findings demonstrate that in vitro screening cannot predict topical efficacy and emphasize the necessity of tissue-based validation before clinical use. Full article

Urban green spaces (UGSs) provide essential ecological services but also accumulate heavy metals (HMs) in their soils, posing a paradoxical health risk through dermal exposure. Traditional risk assessments, based solely on total HM concentrations, often overestimate threats by ignoring bioavailability (the fraction actually absorbed by organisms) and dynamic skin microenvironment factors. This review synthesizes recent advances to propose a precision assessment framework that integrates bioavailability. The framework advocates for the incorporation of bioaccessibility (the fraction of pollutants dissolved in body fluids)-driven exposure metrics (e.g., physiologically based extraction tests), mechanistic dermal permeation models (e.g., Franz diffusion cells, 3D skin constructs), and population-specific susceptibility factors (e.g., children, individuals with compromised skin). We elucidate how soil properties (pH, organic matter) and metal speciation (e.g., Cr(III)/Cr(VI)) modulate cutaneous uptake, and detail toxicological mechanisms including oxidative stress, ferroptosis/cuproptosis, immunotoxicity, and pigmentation disorders. Case studies reveal heterogeneous HM hotspots in high-traffic and densely populated areas, while in vitro–in vivo extrapolation highlights the potential for misestimation in traditional models. Consequently, we discuss the limitations and future directions of this framework, aiming to shift UGS risk management from over-conservative assessment to bioavailability-based precision governance, thereby supporting the health security of sustainable urban habitats. Full article

Background: Hydrolyzed collagen peptides (HCP) are widely used as bioactive ingredients in anti-aging and skin rejuvenation formulations due to their role in supporting skin hydration, elasticity, and extracellular matrix integrity. However, their high hydrophilicity limits effective incorporation into lipid-based systems, and restricts controlled release from formulations. Objective: In this study, ethosomal nanocarriers were designed as a phospholipid–ethanol-based system to promote favorable molecular interactions with hydrophilic peptides, aiming to enhance the encapsulation, stability, and controlled release of HCP for dermocosmetic applications. Methods: HCP-loaded ethosomes were prepared using phospholipid (Lipoid P75) and ethanol and optimized by varying high-pressure homogenization cycles. Physicochemical properties, including vesicle size, distribution uniformity, zeta potential, pH, and long-term stability, were monitored for up to 180 days. Vesicle morphology and peptide–lipid interactions were characterized using cryo-scanning electron microscopy and FTIR spectroscopy. Encapsulation efficiency was determined by ultrafiltration, while cytocompatibility was assessed in HaCaT keratinocyte cells. In vitro release behavior was investigated using Franz diffusion cells and compared with aqueous HCP solutions. Results: All formulations exhibited nanoscale size distribution and high colloidal stability, with negative zeta potentials ranging from −42.9 to −76.7 mV. The optimized formulation demonstrated sustained encapsulation efficiency (73% after 180 days) and preservation of peptide structure, as confirmed by FTIR, indicating effective chemical stabilization within the ethosomal matrix. Cytotoxicity studies confirmed good skin cell compatibility. In vitro release studies revealed a controlled and prolonged release profile from ethosomal carriers compared with free HCP solutions, suggesting improved topical bioavailability of collagen peptides. Conclusions: To the best of our knowledge, this work provides one of the first systematic investigations of optimized ethosomal systems for the stabilization of hydrophilic collagen peptides as anti-aging dermocosmetic ingredients. These findings demonstrate that optimized HCP-loaded ethosomes represent a promising ingredient formulation platform enabling bioactive preservation, formulation stability, and controlled topical performance for collagen-based skin rejuvenation applications. Full article

Isoflavones are plant-derived polyphenols with broad biological activity; however, their application in topical formulations is limited by poor aqueous solubility. The aim of this study was to enhance the aqueous solubility of formononetin using a solvent-free hot-melt extrusion (HME) approach and to enable its incorporation into a hydrogel formulation suitable for skin delivery. Amorphous formononetin-based systems were prepared by HME using polymeric carriers and hydroxypropyl-β-cyclodextrin, with and without prior inclusion complex formation. The resulting formulations were characterized using XRPD, DSC, and FT-IR/ATR to assess amorphization and intermolecular interactions. Aqueous solubility and skin permeability were evaluated using solubility testing, PAMPA, and Franz diffusion cells. The optimized amorphous system exhibited a substantial increase in apparent aqueous solubility compared to crystalline formononetin while maintaining comparable permeability. Cyclodextrin–formononetin interactions were effectively generated during the extrusion process, rendering pre-inclusion unnecessary. The selected system was successfully incorporated into a hydrogel matrix. This study demonstrates that solvent-free HME combined with cyclodextrins is an effective strategy for improving formononetin solubility and enabling its application in hydrogel-based topical delivery systems. Full article

Zeolites are microporous aluminosilicate minerals widely recognized for their adsorption and ion-exchange properties. Their capacity to capture toxic heavy metals has prompted growing interest in their use as anti-pollution agents in skin care formulations. This study investigates zeolite-based creams through an in vitro permeation test using Franz diffusion cells within a Quality by Design (QbD) framework. A 2 × 2 × 2 full factorial design was applied to evaluate the effects of three critical factors: membrane type (Strat-M^® vs. silicone), dosage (10 vs. 20 mg), and dosage regimen. The adsorption and retention of five heavy metals, cadmium (Cd), cobalt (Co), chromium (Cr), lead (Pb), and nickel (Ni), were assessed over 12 h using an in vitro membrane model. The cream containing Zeolite demonstrated significantly higher adsorption of Cr, Co, and Cd compared to placebo and membrane controls, while Ni and Pb exhibited less consistent patterns. No sampling of the receptor compartment was performed; therefore, the analysis focused on metal residues in the donor and membrane compartments. Statistical analyses confirmed the significance of these findings, and graphical trends further supported zeolite’s selective adsorption behavior. Overall, the results provide mechanistic and statistical evidence supporting zeolite as a promising active ingredient for the development of anti-pollution skin care formulations and offer a methodological framework for assessing metal adsorption in topical products. Full article

Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays. The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm² after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups. Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of Staphylococcus aureus. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α. The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis. Full article

Background/Objectives: MHY498, a tyrosinase inhibitor, exhibits poor water solubility, which limits its topical delivery. Despite the importance of solubility data in rational formulation design, comprehensive information on its solubility behavior in various solvents and across a range of temperatures remains limited. Thus, this study aimed to systematically evaluate the solubility characteristics of MHY498 and to develop a nanosuspension formulation using an antisolvent precipitation approach to facilitate the development of an optimized topical formulation. Methods: In this study, we measured the solubility of MHY498 in various monosolvents and diethylene glycol monoethyl ether (DEGME) + water solvent mixtures at 293.15–313.15 K using a solid–liquid equilibrium technique. Based on these solubility data, MHY498 nanosuspensions were prepared via antisolvent precipitation guided by a Box–Behnken design matrix. In vitro skin permeability was also assessed using a Franz diffusion cell system to assess the topical delivery potential of the MHY498 nanosuspensions. Results: Among the investigated monosolvents, MHY498 exhibited the highest solubility in dimethylformamide, dimethylacetamide, DEGME, while the lowest solubility was observed in water. The solubility increased with temperature and DEGME content in solvent mixtures, and the experimental data were well described by thermodynamic and semi-empirical models, indicating an endothermic and spontaneous dissolution process. Solvent–solute interaction analysis revealed that hydrogen-bonding and nonspecific polarity interactions played key roles in enhancing MHY498 solubility. All nanosuspensions prepared within the design space exhibited particle sizes below 150 nm, and the optimized formulation achieved an average particle size of 28.1 nm. The optimized nanosuspension demonstrated a 3.3-fold increase in the cumulative permeated amounts compared with the conventional microsuspension. Conclusions: These findings demonstrate that a rational solvent selection strategy based on thermodynamic solubility analysis and antisolvent precipitation enables effective nanosuspension formulation of MHY498. The DEGME–water system was identified as a formulation-relevant solvent environment that supports both adequate drug solubilization and reproducible formation of nanosized particles. The resulting nanosuspension exhibited favorable particle size characteristics and enhanced formulation feasibility for topical applications. Therefore, it was shown that the developed nanosuspension system, established through a solubility-driven systematic approach, represents a promising strategy for improving topical delivery of MHY498. Full article

Silica spicules provide a natural transdermal conduit but require a linker that binds strongly under physiological conditions and releases payloads selectively in response to biological cues. Existing silane chemistries or polydopamine coatings lack enzyme responsiveness and show limited control over release. We created a 180-member peptide library with the motif L–X1–X2–[Y–F–Y]–A–L–G–P–H–C and screened for silica binding. Biophysical assays (circular dichroism, ζ-potential, quartz crystal microbalance, atomic force microscopy) and molecular dynamics identified high-affinity binders. The lead, P176, was tested for matrix metalloprotease (MMP)-responsive cleavage. Conjugation and release of Vitamin C and Stigmasterol were analyzed by HPLC and Franz diffusion cells. P176 showed high silica affinity (~55 µg mg⁻¹), robust biophysical signals (Δf −35 to −38 Hz; rupture force ~154 pN; ζ shift −22 to−11.5 mV), and favorable adsorption energy (−48.5 kcal mol⁻¹, contact 4.5 nm², 8.5 H-bonds). The MMP gate displayed efficient kinetics (Vmax 117.9 RFU·min⁻¹, Km 5.0 µM) with >90% cleavage at 60 min, reduced to 26% by inhibitor. Conjugation yields reached 87% (Vitamin C) and 77% (Stigmasterol). Franz diffusion showed MMP-dependent release (24 h: Vitamin C 90–96%, Stigmasterol 80–85%) with minimal basal leakage. Released Vitamin C enhanced collagen I to ~250% in fibroblasts, while Stigmasterol attenuated LPS-induced macrophage morphology; keratinocytes retained normal marker expression. This study demonstrates that a single amphipathic, sequence-programmed peptide can couple strong silica anchoring with protease-responsive release and broad payload compatibility, establishing a versatile platform for spicule-based transdermal and regenerative delivery. Full article

Drugs and drug candidate compounds commonly suffer from poor solubility and permeability. One promising strategy to mediate these drawbacks is use of novel solvents, such as deep eutectic compositions. The present research aims to determine the applicability of this approach for therapeutic metal complexes on the example of [Cu(Fur)₂(Phen)] (Fur = furoate-anion, Phen = 1,10-phenantroline) and [Cu(Fur)₂(Neoc)(H₂O)] (Fur = furoate-anion, Neoc = 2,9-dimetyl-1,10-phenanthroline) with molar weight of appx. 500 Da. Interaction of the metal complexes with the deep eutectic solvent (DES) reline was studied using electron paramagnetic resonance (EPR). Minimal inhibitory concentrations of the complexes dissolved in DES and dimethyl sulfoxide (DMSO) were determined and found to be equivalent in both solvents. That is, use of reline as a solvent did not alter the functional properties of the metal complexes. Changes in the transdermal permeation of the complexes in DMSO and DES were assessed using a Franz diffusion cell. It was discovered that depending on the structure of the complex, the permeability might either increase (from 15 to 30%) or decrease (from 13 to 8%) with changes in the solvent, and this can be used to develop dosing strategies. Therapeutic eutectogels were successfully produced by impregnating SiO₂ nanoparticles with the metal complex solution in DES, facilitating convenient topical application. Full article

Background/Objectives: Advancing information on the key physicochemical properties of biologically active substances enables the development of formulations with reduced dosing, lower toxicity, and minimal adverse effects. This work addresses the knowledge gap concerning the pharmacologically relevant properties of harmaline (HML), with a focus on thermodynamic and kinetic aspects. New data were obtained on the compound’s solubility and distribution coefficients across a wide temperature range. Specifically, solubility was measured in aqueous buffers (pH 2.0 and 7.4), 1-octanol (OctOH), n-hexane (Hex), and isopropyl myristate (IPM), while distribution coefficients were determined in OctOH/pH 7.4, Hex/pH 7.4, and IPM/pH 7.4 systems. Methods: Three membranes—regenerated cellulose (RC), PermeaPad (PP) and polydimethylsiloxane-polycarbonate (PDS)—were used as barriers in permeability studies using a Franz diffusion cell. Results: At 310.15 K, the molar solubility of HML in the solvents decreased in the following order: OctOH > pH 2.0 > pH 7.4 > IPM > Hex. The distribution coefficient of HML showed a strong dependence on the nature of the organic phase, correlating with its solubility in the respective solvents. The OctOH/pH 7.4 distribution coefficient ranged from 0.973 at 293.15 K to 1.345 at 313.15 K, falling within the optimal range for potential drug bioavailability. The transfer of HML into OctOH (from either pH 7.4 or hexane) is thermodynamically spontaneous, whereas its transfer into Hex is unfavorable. Conclusions: Based on its permeability across the PP barrier, HML was classified as highly permeable. The distribution and permeation profiles of HML showed similar trends over 5 h in both the OctOH/pH 7.4–PP and IPM/pH 7.4–PDS systems. These systems were therefore proposed as suitable models for studying HML transport in vitro. Full article

Background: Pelubiprofen (PBF) is a cyclooxygenase-2 inhibitor currently marketed as an oral tablet in South Korea. Oral dosing is limited by gastrointestinal variability, first-pass metabolism, which can reduce therapeutic efficiency and increase adverse effects. Transdermal drug-in-adhesive patches provide a noninvasive alternative that bypasses these limitations and enables controlled delivery through the skin. Methods: The solubility of PBF in ethanol was evaluated, and its adhesive compatibility was tested using acrylic- and silicone-based systems. Different drug-loaded formulations were prepared, and their miscibility was assessed. Several permeation enhancers were screened. The physicochemical properties were analyzed. In vitro permeation was studied using rat skin in Franz cells. Accelerated stability was tested at 40 °C and 75% relative humidity for three months. Results: PBF reached near saturation at 120 mg/mL in ethanol. Among the adhesives, Duro-Tak^® 8076 showed the best compatibility with ethanol and PBF. Drug loading above 15% led to crystallization; 15% was selected as the optimal loading. The addition of 2% oleic acid (OA) significantly increased the permeation flux to 11.31 ± 1.50 μg/cm²/h, showing a 3.6-fold enhancement over the control and enhanced deposition in the stratum corneum and dermis. Based on the physicochemical evaluation, PBF was present in an amorphous state within the adhesive matrix. Stability studies revealed no recrystallization, with the drug content maintained at 97–100%. Permeation remained unchanged during storage. Conclusions: The PD-OA2 patch achieved stable drug incorporation, enhanced skin permeation, and robust stability. These findings support the potential of PBF as a clinically relevant alternative to oral PBF formulations for treating localized inflammation and pain. Full article

Background/Objectives: Transdermal formulations are widely utilized in the pharmaceutical and cosmetic fields because they enable non-invasive administration and sustained local drug delivery. Conventional ex vivo skin permeation experiments using Franz diffusion cells have limitations in capturing the spatial and temporal dynamics of skin penetration. This study aimed to develop a confocal laser scanning microscopy (CLSM)-based approach to visualize and semi-quantitatively assess the penetration behavior of fluorescent dyes with differing lipophilicities. Methods: Four fluorescent dyes with different Log P values—Rhodamine B (Rho-B), Rhodamine 123 (Rho-123), Fluorescein Sodium (Flu-Na), and Nile Red (NR)—were formulated into lotion-based vehicles and applied to excised human abdominal skin. CLSM imaging was performed from 10 min to 240 min post-application. Fluorescence intensities were extracted from depth-resolved regions (R1–R4, 30-μm intervals) to examine penetration kinetics and distribution. Results: CLSM imaging demonstrated that Rho-B penetrated through stratum corneum and entered deep into the skin via the hair follicles. Rho-123 and Flu-Na exhibited intercellular and follicular penetration; however, Flu-Na showed only a slight increase in intensity over time; NR showed negligible penetration into the deeper layers. The results of our analysis indicated that moderately lipophilic substances such as Rho-B and Rho-123 diffused deeply into the skin via both transdermal and follicular routes, whereas highly hydrophobic or lipophilic substances remained in the superficial layers. Conclusions: The CLSM-based approach enabled spatially and temporally resolved, semi-quantitative evaluation of transdermal penetration in a single, non-destructive experiment. Although restricted to fluorescent probes, this approach provides a practical early-stage screening tool for comparing route-specific and time-dependent penetration behaviors of compounds with different lipophilicities. Full article