Therapeutic delivery最新文献

Exosomes are naturally occurring extracellular vesicles that have emerged as promising bio-inspired nanocarriers for the treatment of neurological disorders owing to their intrinsic biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier. This review highlights recent advances in exosome biology, cargo-sorting mechanisms, and engineering strategies designed to enhance therapeutic delivery and targeting within the central nervous system. Particular emphasis is placed on the application of engineered exosomes in neurodegenerative diseases, stroke, spinal cord injury, neuropathic pain, and neuroinflammatory disorders. In addition, we discuss how exosomes compare with conventional delivery platforms and critically examine the major barriers limiting their clinical translation, including heterogeneity, scalability, reproducibility, purity, and regulatory standardization. By integrating mechanistic insights with translational perspectives, this review provides a framework for the rational design and future clinical implementation of exosome-based nanomedicines for neurological disorders. Relevant literature was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar. Publications available from database inception through [Month Year] were screened using combinations of keywords including "exosomes," "extracellular vesicles," "neurological disorders," "brain-targeted delivery," "exosome engineering," "drug delivery," and "clinical trials." Additional relevant articles were identified through manual searches of reference lists from selected studies and recent reviews.

Aims: The aims of this study were to develop alginate-based spheroid formulations for the prolonged release of prednisolone acetate, their in vitro and in silico characterization, and identification of formulation key factors influencing drug release behavior.

Methods: Prednisolone acetate spheroids were prepared by extrusion using 2% and 2.5% sodium alginate solutions and different needle diameters. Spheroids containing 30 mg of the drug were filled into gastro-resistant capsules, while controls contained pure drug. Content of prednisolone acetate and calcium, loss on drying, flow properties, dissolution behavior, FTIR spectra, and in silico regional absorption, using GastroPlus were evaluated.

Results: Spheroid formulations with similar drug composition exhibited excellent flowability. Dissolution studies revealed that the release profiles of prednisolone acetate from the produced formulations differ significantly when compared to the pure substance dissolution profile. In silico model predicted the highest absorption rate in the cecum and the ascending colon.

Conclusion: Spheroids derived from sodium alginate have demonstrated the ability to provide prolonged release of prednisolone acetate. Sodium alginate concentration and needle diameter were identified as key formulation factors; their increase enhanced the spheroid resistance to the simulated experimental conditions.

Because of its poor aqueous solubility, low oral bioavailability, extensive cytochrome P450 3A4 (CYP3A4)-mediated metabolism, and acquired resistance, ibrutinib, a first-in-class covalent Bruton's tyrosine kinase (BTK) inhibitor, has shown limited efficacy in solid tumors despite revolutionizing the treatment of B-cell malignancies. Despite growing evidence linking BTK and 65-kDa Bruton's tyrosine kinase isoform (p65BTK) signaling to nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)-mediated tumor progression, immune evasion, and therapeutic resistance, these limitations have limited its therapeutic repurposing in breast, lung, colorectal cancer (CRC), and glioblastoma. While acknowledging the variable clinical applicability of the enhanced permeability and retention (EPR) effect in human tumors, this review critically assesses recent developments in polymeric nanoparticle (PNP)-based delivery systems for Ibrutinib, highlighting their potential to improve drug stability, enable sustained and stimuli-responsive release, enhance tumor accumulation, and facilitate active ligand-mediated targeting. A thorough literature search of PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar found studies published between 2010 and 2026. Preclinical data collectively show that PNPs improve antitumor efficacy, alter the tumor microenvironment, inhibit drug resistance and cancer stemness, lower systemic toxicity, and offer a promising platform for the clinical translation of precision BTK-targeted nanomedicine in solid tumors.

Aim: The isolation efficiency of extracellular vesicles (EVs) is essential to ensure their purity and biological properties. Ultracentrifugation is a traditional method which utilizes high centrifugal forces to separate EVs based on their density. The polyethylene glycol (PEG)-based precipitation method is a scalable and cost-efficient alternative to ultracentrifugation. In this study, two popular techniques used for the isolation of EVs from umbilical cord tissue-derived mesenchymal stem cells (UCT-MSCs): ultracentrifugation and polyethylene glycol PEG-based precipitation methods are examined.

Materials and methods: The UCT-MSCs were cultured in a xeno-free environment using human platelet lysate (hPL) to avoid the risk of xenogenic contamination. The MSCs and EVs were characterized to confirm their physical and functional properties. Cytotoxicity was analyzed in both normal and cancer cells, and the cell migration assay was conducted on cancer cells treated with the EVs to examine the biocompatibility and migratory effects.

Results and conclusions: The similarity in physical, molecular, and functional characterization of UC-EVs and PEG-EVs suggests that PEG-based precipitation maintained the integrity and biological properties of EVs. Overall, the PEG-based precipitation method for EVs isolation is safe and efficient, making them suitable for regeneration and cancer research.

Aim: Oxidative stress (OS) contributes to Alzheimer's disease (AD) pathology. Vitamins C and E target OS, but their efficacies are limited by poor intracellular delivery. Encapsulation in nanovesicles (NVs) may improve targeted delivery for AD treatment.

Methods: Forty-five rats were randomly assigned to nine groups (n = 5 per group): normal control, scopolamine control, vitamin C, vitamin E, vitamin C + E, turmeric NVs (TNV), TNV-C, TNV-E, and donepezil. Treatment was administered intraperitoneally (IP) for one week before induction of the AD-like model using daily IP administration of scopolamine and continued for two weeks. During this time, behavioral activities were conducted, and brain tissues were collected for analysis.

Results: Vitamins C and E showed encapsulation efficiencies of 12.36 ± 1.01% and 55.24 ± 5.82%, with loading capacities of 14.34 ± 1.37% and 40.70 ± 3.52, respectively. TNV-C and TNV-E increased brain levels of vitamins E and C, enhanced antioxidant defense and cognitive abilities, and reduced acetylcholinesterase activity in dementia rats. TNV-C and TNV-E also protected against neuroinflammation and neuritic plaque formation. Vitamin-loaded TNVs were more effective than free vitamins in improving antioxidant status and cognitive outcomes in AD rats.

Conclusion: This study highlights the potential of vitamin-loaded NVs as therapeutics for AD.

Aims: Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with progressive joint damage and pain. The present study aimed to develop and optimize a capsaicin - diclofenac-loaded nanoemulgel incorporating clove and olive oil for enhanced topical delivery and therapeutic efficacy in RA management.

Materials and methods: Central composite design was employed to optimize nanoemulsion composition using oil (5-10%) and Smix (15-20%) as independent variables. The optimized formulation was characterized for particle size, polydispersity index (PDI), zeta potential, transmittance, morphology, rheology, antioxidant activity, cytotoxicity, cell viability, and skin permeation behavior.

Results: Optimized formulation exhibited particle size below 200 nm, PDI below 0.3, zeta potential below -10 mV, and transmittance of 92.6%, indicating good stability. Microscopic studies confirmed spherical globules. The nanoemulgel showed skin-compatible pH and non-Newtonian rheological behavior. Enhanced in vitro permeation, deeper skin penetration, and superior antioxidant activity (76.80 ± 2.90%) were observed compared to the conventional suspension. The formulation also demonstrated higher cytotoxicity against inflammatory U937 macrophage-like cells (58.2% at 50 μg/mL), lower IC₅₀ (28.8 μg/mL), and improved MG-63 cell viability (85.8%).

Conclusions: The developed nanoemulgel demonstrated improved physicochemical characteristics, enhanced skin permeation, and promising anti-inflammatory potential, suggesting its suitability as an effective topical delivery system for rheumatoid arthritis management.

Introduction: Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems.

Areas covered: This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release.

Expert opinion/commentary: Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.

Flavonoids represent one of the most pharmacologically diverse classes of natural polyphenols, demonstrating broad therapeutic potential in oncology, neurodegeneration, cardiovascular, and metabolic disorders. However, their clinical utility has been limited by intrinsic physicochemical deficiencies, including low aqueous solubility, chemical instability, and extensive first-pass metabolism. Traditional formulation strategies have proven inadequate at overcoming these barriers. Nano-enabled delivery platforms circumvent these limitations through rational nanocarrier design, effectively enhancing dissolution kinetics, protecting labile compounds from degradation, and modulating tissue distribution. This comprehensive review critically examines the current landscape of flavonoid-loaded nanoformulations on the recent advancements (2020-2025), with a particular emphasis on cutaneous delivery (topical/transdermal), elucidating formulation-driven mechanisms of bioavailability enhancement. Furthermore, it critically highlights the growing significance of co-delivery approaches of flavonoids with other therapeutic agents or with each other within advanced nanoplatforms in improving therapeutic benefits or diminishing the drug's adverse effects. Nano-engineered delivery platforms effectively neutralize the bioavailability constraints of flavonoids, unlocking their full pharmacological potential and elevating clinical therapeutic efficacy.

Diabetic foot ulcers (DFUs) are serious complications of diabetes, and consist of chronic wound healing, chronic biofilm infection, impaired angiogenesis, oxidized stress, and persistent inflammation. Standard treatments such as systemic antibiotics and growth factors have been found to be ineffective due to poor tissue penetration, degradation and antimicrobial resistance. The aim of this review is to critically analyze advanced strategies for combination therapy using antibiotics, growth factors and/or nanocarriers in order to better manage DFU. Literature was searched in PubMed, Scopus, Web of Science, and Google Scholar databases from January 2010 to March 2026 using keywords related to DFUs, antibiotics, growth factors, nanocarriers, biofilms, and wound healing. Combination nanotherapeutic systems exhibited potential to improve local drug delivery, disrupt biofilms, promote angiogenesis and support tissue regeneration. Stimuli-responsive and sequential-release platforms could enhance therapeutic precision by synchronizing antimicrobial and regenerative functions. Controlled release and modulation of the wound microenvironment are also enhanced by engineering scaffolds and multifunctional biomaterials. Yet the hurdles of biosafety, oxidative cytotoxicity, manufacturing scale-up, regulatory approval, and extended clinical duration remain significant obstacles to translation. Advanced multifunctional nanotherapeutics represent promising emerging strategies for precision-based DFU treatment and may improve infection control, tissue regeneration, and clinical healing outcomes.