Pharmaceutics最新文献

Extracellular vesicles (EVs) are naturally occurring cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. These nano-sized systems, which are derived from a wide range of cell types within an organism and are present in all body fluids. EVs play a crucial role both in health and disease, particularly in cancer and neurodegenerative disorders. Due to their particular structure, they can function as natural carriers for therapeutic agents and drugs, akin to synthetic liposomes. EVs exhibit numerous advantages over conventional synthetic nanocarriers and other lipid-based delivery systems, including their favorable biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. However, EVs' complex characterization and standardization, as well as being more expensive than other vesicular systems, are major drawbacks that need to be addressed before drug loading. The present review introduces the classification of EVs and their physiological roles, currently popular methods for isolating and purifying EVs, the main therapeutic approaches of EV-mediated drug delivery, and the functionalization of EVs as carriers. Consequently, it establishes novel pathways for advancing EV-based therapeutic methodologies across diverse medical disciplines. The study concludes with a discussion of the new challenges and future perspectives related to the clinical application of EVs.

Background: Cardiovascular disease is one of the leading causes of death worldwide. The presence of atherosclerotic plaques in the arteries leads to continuous growth and obstruction of blood vessels, which ultimately leads to acute myocardial infarction and sudden cardiac death. Ultrasound-triggered GVs cavitation has great potential in plaque treatment due to its noninvasive nature and safety. Methods: In this work, we constructed a Hirudin-Gas Vesicle Recombinant Plasmid to achieve gene delivery using macrophage membrane/lipid membrane fusion bio-vesicles. Results: The bio-fusion vesicles retained the macrophage membrane protein integrin α4β1 to combine with vascular adhesion molecules highly expressed by inflammatory cells to achieve delivery; the Hirudin-Gas Vesicle Recombinant Plasmid could escape lysosomes and enter the nucleus to achieve highly efficient transfection; Hirudin and Gas Vesicles are exocytosed through cleavage peptide and exocytosis peptide, respectively; their pharmacological effects are linked and complementary. Gas vesicles can break up lesion plates with the assistance of in vitro ultrasound, and Hirudin achieves fragment ablation and anti-inflammatory and lipid regulation. Conclusions: GVs-HV@MM-Lipo exerts potent anti-atherosclerotic and anti-inflammatory effects with favorable safety. GVs-HV@Lipo reduces mice aortic arch plaque area by 17%, while GVs-HV@MM-Lipo+US achieves further plaque regression and improved hemodynamics. Our work opens up a new paradigm in the treatment of atherosclerosis with Chinese medicine.

Background: Melasma is a chronic skin condition resulting from increased melanogenic activity, which induces a significant emotional impact on the patient's quality of life. The efficacy of melasma treatments depends on individual response and on the chosen therapeutic approach, which may include topical skin-lightening agents, oral drugs, and chemical peels. Objectives: We aimed to evaluate the reported efficacy of treatment techniques on melasma control and patients' quality of life through a systematic review and meta-analysis, as well as to investigate a putative relationship between melasma severity and quality of life. Methods: Following PRISMA guidelines, we collected data from PubMed, Scopus, and Embase databases. The eligibility criteria included studies that analyzed the quality of life through the Melasma Quality of Life (MELASQoL) scale from populations of patients suffering from melasma, scored by the Melasma Area Severity Index (MASI). Results: We retrieved 1296 records; those that did not meet the eligibility criteria and duplicates were excluded, resulting in 41 papers that underwent qualitative analysis (information synthesis), from which 23 papers containing 34 studies were included in the meta-analysis. The meta-analysis revealed a decrease in both MASI and MELASQoL scores following oral or topical treatment, as well as the chemical peeling procedure. Spearman correlation test showed a mild positive relationship between MASI and MELASQoL scores. Conclusions: This study provides evidence supporting oral and topical pharmacological treatments, as well as chemical peels, as effective interventions for melasma management. Despite high heterogeneity among studies and methodological limitations, all treatment modalities analyzed improved patients' quality of life.

Background/Objectives: This study aimed to repurpose aripiprazole (AR), an antipsychotic clinically approved by the FDA, as a novel antifungal drug and to potentiate its therapeutic efficacy through PEGylated terpesomes (PEG-TERs). Methods: PEG-TERs were prepared by thin-film hydration and optimized using a central composite design. The optimum PEG-TER formulation was characterized for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP), and subsequently integrated into polylactic acid (PLA)-based 3D-printed ocuserts. Results: The optimized formulation exhibited spherical vesicles with high EE%, nanoscale PS, narrow PDI, and favorable ZP, alongside excellent stability and mucoadhesive properties. Ex vivo permeation demonstrated a sustained release profile of AR from PEG-TERs compared with an AR suspension, while confocal microscopy confirmed efficient corneal deposition of fluorescein-labeled PEG-TERs. In vivo, the optimum AR-loaded PEG-TERs ocusert exhibited a substantial therapeutic effect in a rabbit model of Candida albicans keratitis, while histopathological assessment confirmed its ocular safety and biocompatibility. Conclusions: In conclusion, AR-loaded PEG-TERs embedded in PLA-based 3D-printed ocuserts represent a promising, safe, and innovative therapeutic platform for the management of Candida albicans-induced corneal infections, offering both drug repurposing and emerging opportunities in advanced ocular drug delivery.

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Background: Turmeric (Curcuma longa) and its main bioactive compound curcumin are widely promoted for cardiometabolic health, yet their efficacy on lipid parameters remains uncertain. Piperine, an alkaloid from black pepper, enhances curcumin bioavailability and may potentiate its effects. This systematic review and meta-analysis aimed to assess the impact of turmeric, alone or combined with piperine, on lipid profiles in adults with metabolic disorders. Methods: A systematic search was conducted (2010-2025) in PubMed, Scopus, and Cochrane CENTRAL. Randomized controlled trials (RCTs) evaluating turmeric supplementation (with or without piperine) on lipid outcomes were included. Methodological quality was assessed with Cochrane RoB 2; certainty of evidence was rated using GRADE. Meta-analyses were performed with random-effects models. The protocol followed PRISMA 2020 guidelines. Results: Ten records were identified; six full texts were assessed; three RCTs (n ≈ 250) were included in quantitative synthesis, and three additional RCTs narratively. Pooled analysis demonstrated significant reductions in triglycerides (WMD -25.5 mg/dL, 95% CI -32.5 to -18.4), total cholesterol (-14.1 mg/dL, 95% CI -22.9 to -5.3), and LDL-C (-17.0 mg/dL, 95% CI -25.2 to -8.8), with an increase in HDL-C (+5.7 mg/dL, 95% CI +2.0 to +9.4). Subgroup analysis suggested greater LDL-C reduction with turmeric+piperine (-29.6 mg/dL) compared to turmeric alone (-16.2 mg/dL). Certainty of evidence was moderate for TG, TC, LDL-C, and low for HDL-C. Conclusions: Turmeric supplementation, particularly when combined with piperine, improves lipid profiles in adults with metabolic disorders. These effects are clinically relevant and comparable to other nutraceuticals, although evidence remains limited by short trial duration and small sample sizes. Larger, long-term RCTs are warranted before turmeric can be recommended in evidence-based dyslipidemia guidelines.

Background: Cultured human skin explants provide preclinical models to investigate drug delivery and the efficacy of topical treatments for wound healing. However, different culture conditions may affect cell viability, proliferation, and even wound healing. Since animal-derived supplements can influence the investigation of human physiological responses, this study evaluated the effects of non-animal supplements on the ex vivo wound healing process to improve the use of this model for preclinical drug efficacy tests. Methods: In in vitro scratch assays using HaCaT cells and fibroblasts, for media supplemented with normal human serum (NHS), oxygen carriers (OCs) had a positive impact on cell migration, supporting the further evaluation in ex vivo skin culture models. Human skin explants with standardized superficial wounds were cultured in four supplemented media: (i) Dulbecco's Modified Eagle Medium High Glucose (DMEM) with fetal calf serum (FCS), (ii) DMEM with NHS and OC, (iii) CnT-Prime^TM with NHS and OC, and (iv) EpiLife™ with NHS and an OC. Results: During the 12-day culture, we observed re-epithelialization in all groups with the exception of EpiLife + NHS + OC (with no Ca⁺⁺ supplement). For these samples, starting from day 6, we noticed a loosening of the dermal-epidermal junction and disruption of the upper epidermal layer. Furthermore, an immunohistochemical analysis of extracellular matrix components and remodeling factors, including type I and III collagen, transforming growth factor-β2, and matrix metalloproteinase-9, provided insights into tissue repair dynamics. Conclusions: NHS plus OC is comparable to FCS supplementation and represents a more physiological and ethical alternative.

Poly (lactic-co-glycolic acid) (PLGA) is a widely used copolymer with applications across medical, pharmaceutical, and other industrial fields. Its biodegradability and biocompatibility make it one of the most versatile polymers for nanoscale drug delivery. The present review addresses current knowledge and recent advances in PLGA-based co-delivery nanoformulations with a special reference to design strategies, functional mechanisms, and translational potential. Conventional and advanced fabrication methods, the structural design of PLGA-based nanocarriers, approaches to scale-up and reproducibility, classification of co-delivery types, mechanisms governing drug release, surface modification and functionalization are all discussed. Special attention is given to PLGA-based co-delivery systems, encompassing drug-drug, drug-gene, gene-gene and multi-modal combinations, supported by recent studies demonstrating synergistic therapeutic outcomes. The review also examines clinical translation efforts and the regulatory landscape for PLGA-based nanocarriers. Unlike most existing reviews that typically focus either on PLGA fundamentals or on co-delivery approaches in isolation, this article bridges these domains by providing an integrated, comparative analysis of PLGA-based co-delivery systems and elucidating a critical gap in linking design strategies with translational requirements. In addition, by emphasising the relevance of PLGA-based co-delivery for combination therapies, particularly in cancer and other complex diseases, the review highlights the strong clinical and translational potential of these platforms. Key challenges, such as reproducibility, large-scale manufacturing, and complex regulatory pathways, are discussed alongside emerging trends and future perspectives. Taken together, this review positions PLGA-based co-delivery strategies as a critical driver for advancing precision therapeutics and shaping the future landscape of nanomedicine.

Background: Frostbite injury is a thermal injury where ice crystals form in skin tissues and subsequently lead to damage due to prolonged exposure to cold temperatures below 0 °C. The extremities are mostly affected, leading to potential amputation. As there is no pharmacological treatment of frostbite injury, we recently reported that non-clinically viable hydrogen sulfide (H₂S) donors promote frostbite wound healing in mice. In this study, we investigated whether commonly used cosmetic creams supplemented with sodium thiosulfate (STS), a clinically viable H₂S donor drug, also promote healing of frostbite wounds. Methods: Frozen magnets (-80 °C) were placed on the dorsal skin of 40 C57BL/6 mice for 3 min to induce frostbite injury. Next, commercially available cosmetic creams (Aveeno, Dove, Neutrogena, and Nivea) were topically applied on frostbite wounds daily for 14 days with or without 150 µM of STS supplementation. The mice were sacrificed on day 15 after induction of frostbite injury, and samples of the injured dorsal skin tissue were collected for analysis. Results: Addition of STS enhanced frostbite wound healing, as evidenced by progressive and significantly reduced wound area by about 50% and inflammation (p < 0.05), and markedly increased granulation tissue formation by >45%, fibroblast maturation by >28%, and re-epithelialization by >63% compared to control groups (p < 0.05), with Nivea producing a superior wound-healing effect. Also, STS supplementation significantly upregulated the expression of CD31 (by >25%), KI-67 (by >25%), CD163 (by >20%), fibronectin (by >14%), and cytokeratin (by >50%) in frostbite wounds compared to control groups, with Aveeno and Nivea producing a better wound-healing effect than Dove and Neutrogena creams. Conclusions: In conclusion, STS accelerated healing of frostbite wounds. Therefore, it could be considered as a novel pharmacological treatment of clinical frostbite.

Background: Nanomedicine has demonstrated great potential to improve drug delivery across various diseases. However, accurately monitoring the real-time trafficking of organic nanoparticles (NPs) within biological systems remains a significant challenge. Current detection methods rely heavily on fluorescence, while high-resolution, label-free imaging is often precluded by the limited optical contrast of organic materials, limiting a comprehensive understanding of NP fate. Metallic doping allows simultaneous detection of carriers using multiple imaging and analysis techniques. This study presents a novel approach to prepare gold-doped hybrid NPs compatible with multimodal imaging, thus facilitating multimodal tracking. Methods: Gold-doped NPs were successfully synthesized via nanoprecipitation, yielding stable, monodisperse carriers with optimal size, confirmed by Dynamic Light Scattering and Nanoparticle Tracking Analysis. UV/Vis spectroscopy confirmed effective gold-doping, with doping efficiency of approximately 50%. Transmission Electron Microscopy (TEM) showed gold NP accumulation throughout the polymer core and near the lipid shell. Results: Although gold doping resulted in a slight increase in NP size and zeta potential, no effects on cytocompatibility or cellular uptake by glioblastoma and microglia cells were observed. Furthermore, the optical properties (i.e., the refractive index and the UV spectrum) of the NPs were successfully modified to enable tracking across complementary imaging modalities. Real-time, label-free visualization of NP accumulation in the cytoplasm of U87 cells was achieved via holotomography by exploiting the enhanced refractive index after gold-doping. This observation was confirmed through correlation with fluorescence confocal microscopy, using fluorescently labelled gold-doped NPs. Furthermore, the high electron density of the gold tracer facilitated the precise localization of NPs within intracellular compartments via TEM, bypassing the inherently low contrast of organic NPs. Conclusions: These findings validated the gold-doped NPs as versatile nanoplatforms for multimodal imaging, showcasing their potential for non-invasive, high-resolution tracking and more accurate quantification of intracellular accumulation using diverse analytical techniques.