Search Results (492)

The integration of exosomes into professional cosmetics marks a significant paradigm shift from traditional passive formulations to advanced regenerative esthetics. Rather than being defined solely by their nanometric dimensions or classical association with endosomal biogenesis, these vesicles function as highly targeted intercellular messengers capable of delivering complex bioactive payloads to modulate tissue repair and collagen synthesis. While robust preclinical and clinical trials validate their remarkable potential in skin rejuvenation, hair restoration, and hyperpigmentation management, significant translational barriers remain. A critical analysis of the current literature reveals that successful clinical outcomes frequently rely on physical penetration enhancers, such as microneedling or fractional lasers, making it challenging to isolate the autonomous efficacy of topical vesicles from the trauma-induced regenerative response. Furthermore, commercial viability is dictated by stringent regulatory frameworks. In the European Union, Regulation (EC) No 1223/2009 strictly prohibits human-derived biologicals, while the US Food and Drug Administration (FDA) aggressively monitors the unsubstantiated marketing of cellular therapies. To navigate these biosafety and legal constraints, the aesthetic industry is increasingly pivoting toward non-human and legally compliant alternatives. Consequently, Plant-Derived Extracellular Vesicles (PDEVs), microbiome-derived exosomes (such as those obtained from bacterial fermentation), and bioengineered synthetic analogues have become the focal point of market innovation. A practical evaluation of the MCCM Medical Cosmetics portfolio illustrates this strategic shift, demonstrating the clinical versatility of botanical sources. To secure the long-term credibility of exosome technology, the industry must overcome current manufacturing heterogeneity by aligning with international standardization frameworks, such as the MISEV2023 guidelines, thereby ensuring reliable delivery systems, batch-to-batch consistency, and uncompromised consumer safety. This review provides a comprehensive overview of the biological mechanisms, clinical efficacy, and translational challenges associated with exosome-based cosmetics. Full article

Background/Objectives: BPC-157 (body protection compound 157) is a synthetic pentadecapeptide derived from a gastric protein fragment with reported cytoprotective and regenerative properties across multiple organ systems. Despite over three decades of preclinical research demonstrating consistent biological activity, its pharmaceutical development remains rudimentary, with no approved formulation, no validated dosing regimen, and no completed Phase II clinical trial. This review critically evaluates BPC-157 from a biopharmaceutical and drug development perspective, examining its physicochemical and pharmacokinetic properties, formulation challenges across routes of administration, the pharmacokinetic–pharmacodynamic disconnect that characterizes its preclinical profile, and the regulatory and translational barriers that currently preclude clinical advancement. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE, Embase, and Cochrane Library from database inception to April 2026. Search terms included “BPC-157”, “BPC157”, “body protection compound 157”, “pentadecapeptide”, and “GEPPPGKPADDAGLV”, each combined with “pharmacokinetics”, “formulation”, “biopharmaceutics”, “drug delivery”, “clinical trial”, “toxicology”, and “regulatory”. Patent databases (Espacenet, Google Patents) and regulatory agency websites (FDA, EMA, WADA) were searched independently. Searches were supplemented by forward and backward citation tracking of key references. Articles were selected based on relevance to biopharmaceutical characterization, pharmacokinetics, formulation science, clinical evidence, and regulatory status; pharmacodynamic studies were included insofar as they inform translational development. Evidence was synthesized with emphasis on pharmaceutical characterization, formulation science, and translational feasibility; no formal quality assessment instrument was applied, consistent with the narrative review design. Results: BPC-157 exhibits unusual stability in gastric juice and demonstrates activity via oral, parenteral, and topical routes, yet its human pharmacokinetic profile remains critically undercharacterized despite a recently published formal preclinical ADME study in two species confirming a sub-30-min plasma half-life, linear dose-proportional kinetics, and intramuscular bioavailability of 14–51% depending on species. A plasma half-life of under 30 min—confirmed preclinically and in a preliminary two-subject human pilot—contrasts with prolonged biological effects lasting hours to days—a disconnect with significant implications for dosing strategy and formulation design. No pharmaceutical-grade formulation has been developed or validated. The peptide lacks bcs classification data, permeability characterization, and formal excipient compatibility studies. Available clinical data derive from fewer than 30 subjects across three uncontrolled pilot studies, none of which employed standardized pharmaceutical preparations. Conclusions: BPC-157 presents a compelling but pharmaceutically underdeveloped profile. The primary barrier to clinical translation is not the absence of biological activity, but the absence of fundamental pharmaceutical science: characterized formulations, validated pharmacokinetics, and a coherent drug development strategy. Addressing these biopharmaceutical gaps is a prerequisite for any meaningful clinical program. Full article

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

This study aims to develop and systematically evaluate a new lipid-based formulation of blueberry anthocyanins, which can accelerate the healing effect of the cornea. The study first successfully screened and optimized the formulation and preparation process for blueberry anthocyanin liposomes. Characterization via transmission electron microscopy and dynamic light scattering revealed uniformly distributed, near-spherical liposomes with distinct phospholipid bilayers. Key physicochemical parameters—particle size, zeta potential, encapsulation efficiency, and drug loading capacity—all met formulation standards. In vivo pharmacodynamic experiments demonstrated that topical administration of blueberry anthocyanin liposomes significantly accelerated the repair process and effectively mitigated depressional damage to the corneal epithelium in a New Zealand white rabbit corneal injury model induced by 10.6 μm mid-infrared CO₂ laser. In summary, the blueberry anthocyanin liposomes successfully prepared in this study exhibit excellent performance, effectively enhancing drug exposure levels in vivo and promoting corneal repair. This provides reliable experimental evidence for the development of plant natural active ingredients in ophthalmic treatments. Full article

Background: Apremilast (APM) is a selective phosphodiestrase-4 (PDE-4) inhibitor currently administered orally for the treatment of psoriasis. However, gastrointestinal irritation, frequent dosage regimens, and patient noncompliance limit its oral administration. Additionally, the poor permeability and solubility of APM make dermal administration challenging. Objective: The current study aims to formulate an optimized APM-loaded nanoemulsion formulation (APM-NE) to enhance drug delivery to deep psoriatic skin layers, thereby increasing dermal drug concentration for the effective treatment of psoriasis. Method: Using the phase titration method, the nanoemulsion (NE) was made with Capryol 90, Tween 20, and Labrasol as oil, surfactant, and co-surfactant, respectively. Results: The optimized formulation (F5) exhibited favorable physicochemical properties: mean droplet size of 147.4 ± 2.4 nm, and an entrapment efficiency (EE) reaching 86.30 ± 2.54%. TEM confirmed spherical, uniformly distributed droplets. In vitro release (86.1 ± 0.24%) followed zero-order kinetics. To enhance skin retention, F5 was incorporated into 2% Carbopol 980 gel, yielding F5G with pseudoplastic flow. Ex vivo permeation showed significantly higher drug delivery for F5 (1266.50 ± 5.6 µg/cm²) and F5G (1057.7 ± 6.76 µg/cm²) compared to crude APM gel (CR-APMG). In vivo, the inhibition of edema in rat paws was highest with F5G (66.83 ± 0.23%). RAW 264.7 cell studies showed 92.37% nitric oxide inhibition, and histopathology confirmed reduced inflammation. Conclusions: These results support APM-NE gel as a promising topical strategy for psoriasis therapy. Full article

Optimizing drug administration remains a central challenge in the development of modern therapies, especially in the context of conditions that require spatiotemporal control of active substance release. In this context, hydrogels have been intensively investigated as polymeric platforms for drug delivery, through their three-dimensional hydrophilic structure, tunable properties, and compatibility with biological environments. This analysis presents an integrated approach to hydrogels used in drug administration, addressing the physicochemical fundamentals, the constitutive polymeric materials, and the mechanisms of response to relevant physiological stimuli. Recent experimental studies have been discussed, which highlight the use of hydrogels based on natural, synthetic, and hybrid polymers for controlled and targeted release, in correlation with various administration routes, including oral, injectable, transmucosal, and topical ones. Advanced functionalization strategies that allow adaptive responses to pH, temperature, glucose, enzymes, and reactive oxygen species are also analyzed. Furthermore, emerging directions integrating hydrogels with biosensors, microdevices, and wireless communication systems for real-time monitoring and on-demand release are highlighted. Overall, the analysis emphasizes the role of smart hydrogels as multifunctional platforms for complex therapeutic strategies while also underlining the current challenges associated with clinical translation and long-term performance. Full article

Background/Objectives: Antimicrobial peptides (AMPs) represent a promising class of therapeutics with diverse biological functions, including antibacterial, anti-fungal, anti-parasitic and anti-tumoral activities. Previous works demonstrated the successful repurposing of the two synthetic AMPs 19-2.5 and 19-4LF for cutaneous leishmaniasis, when the compounds were administered in solution on skin lesions caused by Leishmania major in a BALB/c mouse model. In this research project, we assessed the activity of 19-4LF, 19-2.5, and their hybrid 19-2.5LF derivative when formulated as a cream for topical administration in the same animal model. Methods: The peptides were formulated in DAC cream and applied to the wound of BALB/C mice for 30 days. Lesion progression was monitored using a digital caliper. Parasite burden was measured by qPCR. Parasite viability was assessed using MTT and microscopy imaging assays. Results: The three peptides in cream formulation succeeded in reducing the skin lesion. Peptide 19-4LF was the most potent, followed by 19-2.5LF and then 19-2.5. In addition, 19-4LF was able to significantly reduce the parasite burden in the skin lesions of infected mice, as measured by quantifying L. major Lm18S ribosomal gene mRNA levels using qPCR. Moreover, when combined, the peptides exhibited synergistic effects on L. major promastigotes and significantly reduced the number of amastigotes in infected macrophages. Conclusions: These studies support the approach of repurposing these AMPs as antileishmanial drugs and identify 19-4LF as a lead candidate for further studies. While historical barriers to peptide therapeutics included high production costs, recent advancements in biological fermentation and synthesis strategies have significantly improved their economic viability. Furthermore, the use of nanotechnology delivery systems can reduce the required dosage, further making peptide therapy a sustainable option for neglected diseases, including leishmaniasis. Full article

Background/Objectives: For successful wound management, dressings must be maintained in a moist environment to optimally enhance the microenvironment of the wound and efficiently deliver bioactive agents. Sodium humate has demonstrated potential wound-healing activity, although its topical delivery is still a challenge. This study aimed to develop and optimize polysaccharide-based dermal patches incorporating sodium-humate-loaded transferosomes and to assess their physicochemical and wound-healing properties. Methods: Transferosomes were obtained via thin-film hydration and prepared utilizing the Taguchi experimental design based on the impact of lipid content, lipid-to-surfactant ratio, and lipid-to-drug ratio on vesicle size, ζ-potential, and drug entrapment efficiency. The optimized transferosomes were loaded into alginate/HPMC composite dermal patches prepared through solvent evaporation. Results: The optimized transferosome formulation had an average size of 250.9 ± 2.3 nm, a ζ-potential of −3.57 ± 0.25, a high deformability of 93.01 ± 2.41%, and an effective drug-entrapment efficiency of 30.13 ± 1.04%. The use of transferosomes greatly affected patch thickness, moisture content, and surface morphology. A biphasic drug release profile of sodium humate was demonstrated via an in vitro release study, showing an initial burst followed by sustained drug release within 6 h. In vivo evaluation of transferosome-loaded patches showed that the formulations were able to effectively promote wound healing compared with the control. Conclusions: The developed transferosome-embedded alginate/HPMC dermal patches constitute a promising platform for the controlled topical administration of sodium humate and show promising enhancement of wound healing. Full article

Background: Pentamidine isethionate (PTM) and miltefosine (MF) are clinically relevant antiparasitic agents whose use is limited by toxicity, emerging resistance, and the lack of effective co-delivery strategies. Tetronic^® 1307 (T1307), an amphiphilic and thermoresponsive block copolymer, was investigated as a carrier to enable their combination therapy. Methods: PTM and MF were formulated in T1307-based micelles and thermoresponsive gels. The systems were characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance spectroscopy (NMR). Antiparasitic activity was evaluated against Leishmania major promastigotes. Results: MF formed stable micelles that efficiently incorporated PTM, generating a “drug-in-drug” architecture. While T1307 alone showed limited PTM loading, MF promoted mixed micelle formation and enhanced PTM incorporation. At physiological temperature and adequate copolymer concentrations, drug-loaded micelles formed thermoreversible gels suitable for topical application. The combined formulations preserved drug activity and exhibited synergistic effects against L. major. Conclusions: T1307 is a promising platform for the co-delivery of PTM and MF, enabling synergistic combination therapy and thermoresponsive gel formation with potential to reduce systemic toxicity and improve treatment administration. Full article

Nuclear medicine is a medical specialty combining parenteral radioactive drug handling and complex clinical workflows, making systematic process-related incident (PRI) analysis essential to support healthcare quality improvement. This study reports a four-year single-center retrospective analysis of PRIs in a nuclear medicine department and describes the development and implementation of a scenario-based radiopharmacy training program for nuclear medicine technologists (NMTs) derived from these findings. PRIs were extracted from the institutional reporting system and categorized according to a structured classification. Training scenarios were designed from recurrent radiopharmacy-related PRIs, and their impact was evaluated using a knowledge questionnaire administered pre and post training. A total of 223 PRIs were analyzed, of which 38.6% (n = 86) were related to the radiopharmaceutical circuit. Among these, 28.3% occurred exclusively within the radiopharmacy cleanroom. Administration (19%), dispensing (15%), delivery and reception (15%), and preparation and quality control (15%) of radiopharmaceuticals were the most frequently involved stages. No PRI exceeded a moderate criticality level. Eight NMTs participated in the training program, consisting of an analysis of videos depicting the developed scenarios. The mean knowledge score increased significantly from 7.51/10 before training to 8.46/10 four weeks after training (p = 0.02), with marked improvements in hygiene- and radioactivity-related topics. These results support the use of retrospective PRI analysis as an operational basis for specific, scenario-based training to strengthen safety practices in radiopharmacy settings. Full article

Skin cancer is among the most common malignancies worldwide, posing a significant societal burden due to its increasing incidence and its limited responsiveness to conventional topical therapies. Treatment is challenged by the presence of the skin barrier which restricts drug penetration. This review discusses the structural and physiological challenges of topical delivery and summarizes efforts to develop functional biomaterials to enhance skin drug penetration. Important aspects to consider when developing formulation strategies, such as drug properties and release mechanisms, are discussed alongside current limitations and future perspectives. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

Background/Objectives: Cutaneous leishmaniasis (CL) remains a global health challenge, with treatment options often limited by drug resistance and systemic toxicity. Amphotericin B (AmB) represents a promising alternative. but intravenous administration causes severe systemic adverse effects. Despite growing interest in topical therapies, knowledge gaps remain regarding the comparative efficacy of delivery systems, including the influence of treatment timing and potential intrinsic effects. This study aimed to develop and characterize different topical AmB formulations (polymeric nanoparticles (PCL-AmB), a lipid-based (Oil_AmB) formulation, and a gel emulsion) to evaluate their in vivo efficacy against CL in a murine model, considering treatment initiation timing and potential intrinsic effects of the delivery systems. Methods: Formulations were prepared and characterized in terms of hydrodynamic size, polydispersity index, and AmB content. Antileishmanial activity was assessed in two independent in vivo experiments, with topical monotherapy administered five days per week for four weeks, starting either 10 or 30 days post-infection, representing early and established chronic stages of infection, respectively. Results: All formulations exhibited nanoscale dimensions and high homogeneity, with the lipid system demonstrating superior AmB solubilization. Both PCL-AmB and Oil_AmB reduced parasite load in the footpad, with Oil_AmB also reducing parasite load in draining lymph nodes. Conclusions: PCL-AmB and Oil_AmB reduced lesions and parasite burden in L. amazonensis-infected mice. Treatment timing was critical, with early Oil_AmB also reducing parasite loads in draining lymph nodes. These findings suggest that topical AmB formulations may provide a promising alternative for CL treatment, though further studies are required to optimize efficacy and administration schedules. Full article

Natamycin, a polyene macrolide antifungal, has long been used as a food preservative and is the only Food and Drug Administration (FDA)-approved topical treatment for fungal keratitis. While its safety is supported by specific ergosterol interaction and minimal systemic absorption, current research mainly focuses on short-term effects, often overlooking long-term, developmental, and microbiome-related impacts. In food applications, questions remain about cumulative exposure and potential disruptions to gut microbiota. For ophthalmology, advanced delivery methods like nanocarriers and hydrogels enhance drug penetration but may alter pharmacokinetics and pose formulation challenges. Regulatory approvals have historically depended on established safe use and limited toxicological data, emphasizing the need for more systematic evaluations. Zebrafish (Danio rerio) represent a promising yet underutilized model for addressing significant gaps in research, particularly in the realms of microbiome studies, ocular health, developmental processes, and multigenerational effects. When paired with omics technologies, zebrafish facilitate comprehensive system-level mapping of drug-induced outcomes. This review consolidates existing evidence and positions zebrafish as a vital translational link between in vitro assays, mammalian models, and clinical practice. Additionally, it proposes a framework to ensure the effective and scientifically supported use of natamycin in both food and medicinal applications. Full article

Background: Lidocaine, classified as an amide-type agent, and tetracaine, designated as an ester-type agent, are frequently co-formulated for dermatologic procedures. Despite the extensive literature on the pharmacokinetics (PK) of these substances, there is a paucity of head-to-head comparisons of intravenous (IV) and topical administration in the same preclinical model. Absolute bioavailability (F%) is imperative for optimizing formulation design and safety. Methods: A single-dose, single-sequence, three-period pilot study was performed in male Göttingen mini-pigs. The first period of the study involved the intravenous bolus administration of lidocaine HCl and tetracaine HCl, with a dosage of 1 mg/kg for each agent. In Period 2, the topical application of Pliaglis (a combination of 7% lidocaine and 7% tetracaine, with a concentration of 10 g/100 cm² and a duration of 60 min) was utilized. In Period 3, the pharmacokinetic profile of Z4T4L4 (a formulation comprising 4% lidocaine HCl and 4% tetracaine HCl) was assessed under the same experimental conditions. Blood samples were collected up to 24 h after the administration of the drug; skin biopsies were obtained 90 min after the application of the test substance. Plasma and skin concentrations were measured by means of validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). PK parameters were derived using a noncompartmental analysis approach, while F% was calculated through AUC comparison with IV dosing. Results: Subsequent to intravenous administration, the mean elimination half-lives of lidocaine and tetracaine were determined to be 1.62 h and 1.85 h, respectively. Pliaglis demonstrated higher skin concentrations of lidocaine (358 μg/g) and tetracaine (465 μg/g) compared to Z4T4L4 (33.6 μg/g and 46.1 μg/g, respectively). Despite lower skin levels, Z4T4L4 produced higher F% (lidocaine: 1.98% vs. 1.41%; tetracaine: 3.34% vs. 1.26%). The time to maximum plasma concentration (T_max) for lidocaine was found to be 2–4 h (Pliaglis) and 2–8 h (Z4T4L4), while for tetracaine, it was 1–8 h (Pliaglis) and 2–8 h (Z4T4L4). Conclusions: In this preliminary study, which included three subjects, Z4T4L4 exhibited a numerical tendency towards increased systemic bioavailability in comparison with Pliaglis. This observation was noted despite the fact that Z4T4L4 resulted in markedly lower skin concentrations. Due to the exploratory nature of the pilot study (n = 3), observed differences are reported as numerical trends. The data suggest that Z4T4L4 may enhance systemic absorption while reducing skin retention, highlighting a potential formulation-dependent dissociation between local concentration and systemic bioavailability. These preliminary findings provide in vivo evidence of a divergence between eutectic-based tissue retention and enhancer-driven systemic flux. This highlights that formulation design fundamentally dictates the safety profile of local anesthetics, necessitating a balance between local efficacy and systemic safety. Full article