Drug Delivery最新文献

The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of Staphylococcus, Streptococcus, and Corynebacterium as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing in vivo. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.

Receptor-mediated transcytosis (RMT) represents a promising strategy for delivering macromolecular and colloidal therapeutics across the blood-brain barrier (BBB). However, mechanistic elucidation of RMT remains limited by the difficulty of visualizing subcellular trafficking pathways. Conventional imaging approaches either lack sufficient spatial resolution or require costly, technically complex instrumentation. Here, we report a cell swelling and upright mounting-based (CSUM-based) imaging approach that reorients the Z-axis into the high-resolution XY-plane using standard confocal microscopy, enabling direct RMT visualization without computational reconstruction or specialized hardware. We tracked intracellular trafficking of transferrin (Tf) and anti-transferrin receptor antibody (anti-TfR Ab) as model cargos using our CSUM-based imaging approach via compartment-specific markers and time-resolved co-localization analysis. This approach resolved cargo-containing vesicles traversing from the apical to basolateral membranes. Tf completed transcytosis within 15 min, whereas anti-TfR Ab initially entered the endolysosomal pathway before rerouting to transcytosis under receptor saturation conditions. The CSUM approach provides a simple yet effective platform for high-resolution visualization of membrane transport and vesicle dynamics, offering broad applicability to drug delivery research and the design of brain-targeted therapeutics.

By 2050, more than 61 million people worldwide are expected to lose their vision due to conditions like age-related macular degeneration, glaucoma, diabetic retinopathy, and uveitis (Bourne et al. 2021). This anticipated rise highlights the urgent need for more effective treatment options. While progress continues in developing new pharmacological agents, treating ocular diseases with these therapies remains particularly challenging due to the eye's unique and complex anatomy. This is largely due to the limitations of current drug delivery methods, including systemic administration, topical delivery application, transscleral/periocular drug delivery, and intravitreal injections, which are associated with low bioavailability, side effects, and rapid drug clearance. Given these challenges, microneedles have emerged as a promising alternative. Their minimally invasive nature and ability to precisely target the anterior and posterior segments make them well suited for enhancing therapeutic outcomes while reducing systemic exposure and potential side effects, as well as improving patient adherence (Kang-Mieler et al. 2017; Gadziński et al. 2022). The purpose of this review is to discuss recent advancements, key challenges, and strategies for microneedle-based ocular drug delivery systems, with an emphasis on their potential to treat both anterior and posterior eye diseases.

Proniosomes represent an advanced composite vesicular platform that integrates non-ionic surfactants, lipids, and biodegradable carriers to significantly improve drug solubility, stability, and transmembrane delivery. These dry powdery formulations are transformed into multiscale niosomes upon contact with a hydrated medium to achieve controlled release and enhanced drug permeability. This seminal review delineates the transformative potential of proniosomal systems in treating various diseases, detailing diverse routes of administration, formulation techniques, mechanisms of action, as well as their advantages and limitations. Proniosomes address major issues such as systemic toxicity, poor solubility, and erratic absorption while maintaining green chemistry principles owing to their biodegradable constituents. By critically analyzing the potential for industrial translation, this review highlights the knowledge gap on clinical studies, scalability, and regulatory issues. The translation potential has even been further enhanced by recent developments in bioconjugation and nanotechnology, such as ligand-anchored proniosomes that enable active targeting. The topic's relevance is evident, as proniosomes complement next-generation biotechnology tools, such as mRNA delivery, while offering a sustainable alternative to liposomes. By compiling the most recent data, this review strives to catalyze innovation in novel drug delivery, making it essential for researchers and pharmaceutical developers.

Currently, increasing attention is being paid to the extraction and utilization of materials with special biological activities in nature or for medical applications. Owing to their unique biological characteristics and diverse application potential, microalgae are among the most promising materials in the field of biomedicine. Because of their diverse morphology and readily functionalizable surface, they can efficiently carry drugs and achieve targeted drug release. This can avoid major challenges of other methods related to toxicity, biocompatibility, and immunogenicity, which is important for the treatment of various diseases, particularly those related to hypoxia. Despite the distinct advantages of microalgae over other biomaterials, several challenges persist in their practical application. Herein, we comprehensively describe the current state of research on the microalgae drug-delivery system (MDDS). In particular, we explore various microalgae-based strategies and methods to improve the load capacity and stability of DDS, and to achieve target positioning and tracking. With further research on microalgae, their application prospects in DDSs will broaden. In the future, researchers will continue to explore the features and advantages of microalgae; develop more efficient, safe, and accurate DDSs; and provide more options for clinical treatments. Continued progress in microalgal cultivation technology and reduction in large-scale production costs will expand the clinical applications of MDDSs.

Artocarpus altilis methanolic extract (AAM) exhibits potent protective effects against particulate matter (PM)-induced skin damage; however, its poor aqueous solubility and limited skin permeability restrict its topical bioavailability. To overcome these limitations, we developed a polymer-based drug delivery system by fabricating electrospun nanofibers composed of polyvinylpyrrolidone (PVP), hydroxypropyl-β-cyclodextrin (HPBCD), and AAM. The optimized formulation engineering strategy enhanced AAM solubility via increased surface area, reduced crystallinity, and hydrogen bonding interactions with HPBCD/PVP. The nanofiber matrix also provided an occlusive effect, improving skin hydration and facilitating transdermal diffusion through the stratum corneum. In vitro studies demonstrated improved cellular uptake, greater permeability, and enhanced antioxidant activity, leading to superior anti-pollution efficacy compared to raw AAM in a PM-induced HaCaT keratinocyte model. These results highlight AAM-loaded electrospun nanofibers (ANFs) as a biodegradable, and environmentally sustainable platform for delivering plant-derived bioactive ingredient, offering high potential for advanced topical formulations targeting pollution-induced skin aging.

Mesoporous silica nanoparticles (MSNs) have garnered significant attention across various disciplines, including chemistry, physics, and materials science, owing to their distinctive properties and functionalities. Numerous studies have demonstrated that MSNs possess several advantageous characteristics, such as tunable pore sizes, excellent biocompatibility, and a high specific surface area. These attributes render mesoporous silica nanoparticles promising for diverse applications in medical fields, including in vivo targeting, drug delivery, and disease diagnosis. Nevertheless, recent research has indicated that mesoporous silica may induce cellular and tissue toxicity in humans, necessitating further evaluation of its long-term safety. Additionally, parameters such as the shape, particle size, and surface modification of MSNs require careful control to enhance their biodegradability, regulate the circulation time of nanomaterials within the body, and mitigate the immunogenicity of mesoporous silica, thereby facilitating the clinical translation of mesoporous silica nanoparticles. This article reviews the advancements in research concerning the use of mesoporous silica nanomaterials in targeted therapy, drug delivery, and tissue engineering. This work evaluates the potential applications of mesoporous silica materials in the biomedical sector and delineates future research directions for MSNs by examining and summarizing their biological toxicity and associated risks.

Current clinical strategies for Methicillin-resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI) predominantly focus on single-approach interventions such as anti-inflammatory therapy. However, due to the complex, multi-pathway pathological network underlying the disease, targeting a single pathway often yields suboptimal therapeutic outcomes. Consequently, there is a pressing need to develop innovative drug delivery systems capable of systematically addressing this intricate pathological process. Geraniol, a naturally derived monoterpene alcohol, exhibits multiple pharmacological activities including antimicrobial, antioxidant, and organ-protective effects, while the antimicrobial peptide (AMP) FK13-a1 demonstrates broad-spectrum antibacterial, anti-inflammatory, and immunomodulatory functions. Recognizing their complementary mechanisms of action, we innovatively propose a synergistic therapeutic strategy combining geraniol with FK13-a1. To enhance targeting precision, we engineered a biomimetic delivery system by coating nanomaterials with macrophage membranes via tyramine linkage, enabling specific homing to pulmonary inflammatory sites. Guided by this design concept, we successfully fabricated the biomimetic nanodrug Tyr-MM@PLGA/G+F and conducted systematic characterization using multiple analytical techniques. Through established in vitro and in vivo infection models, we evaluated the therapeutic efficacy of this nanosystem. Results demonstrated that Tyr-MM@PLGA/G+F actively targets ALI lesion sites, achieving precise co-delivery and synergistic action of geraniol and FK13-a1 at the pathological foci, thereby significantly enhancing treatment outcomes. This study not only validates the remarkable efficacy of this composite nanosystem against ALI but also provides novel insights and experimental evidence for targeted therapy of this condition.

Although numerous drugs have been developed for intravaginal administration, the implementation of personalized intravaginal treatment options is limited. The MedRing overactive bladder (OAB) system is a medical device for intravaginal oxybutynin administration via patient-controlled schedules. The primary aim was to assess the feasibility, tolerability, and safety of intravaginal oxybutynin administration via the MedRing OAB system. Second, the functioning of the MedRing OAB system, user satisfaction and quality of life (QoL) were assessed. Female OAB patients were included to receive the MedRing OAB system. Treatment was divided into three periods with increasing dosing flexibility: 2 mg at three fixed timepoints daily, 2 mg at three patient-defined timepoints daily, and flexible dosing up to 6 mg/day of 1 or 2 mg doses. Feasibility, tolerability, satisfaction, and QoL were assessed via questionnaires, safety via treatment-emergent adverse events (TEAEs), device deficiencies (DDs) and physical examination and functioning via pharmacokinetics and MedRing logs. Thirteen patients were enrolled, of whom three patients discontinued the study prematurely. Most patients reported low user burden, found the system practical and expressed positive opinions. The TEAEs were consistent with known oxybutynin effects and local TEAEs were comparable to other intravaginal devices. Most DDs were synchronization difficulties, which improved after a software update. After 10 minutes, oxybutynin levels were detected in 12 of the 13 patients. This study showed that the MedRing OAB system appears to be a feasible, tolerable and safe alternative intravaginal oxybutynin administration for 28 days in OAB patients, offering a potential alternative to existing treatment options and introducing personalized patient care.

The instability of liposomes in blood samples during clinical drug research and drug monitoring results in the inability to accurately determine the actual drug concentrations in the body at the time of collection, mainly due to lipid deterioration, particle fusion or aggregation, and phase separation degradation, resulting in payload leakage. To improve drug monitoring accuracy, we developed a cryopreservation strategy in this study by innovatively combining cryoprotective agents (CPAs), such as L-proline, sucrose, and polyvinyl alcohol (PVA), to prevent liposomal leakage and maintain stability for reliable drug monitoring and clinical drug research applications. Doxorubicin liposomes were prepared, and the CPAs were tested at various concentrations and under different freeze‒thaw protocols in biological matrices, with the stability and leakage of the liposomes assessed. Each CPA contributes distinct stabilization mechanisms, with L-proline's osmoprotective ability, sucrose's hydrogen bonding, and PVA's steric hindrance to form a protective barrier. The optimized CPA combination demonstrated superior performance at 85% (v/v) by preserving liposomal integrity, offering the best cryoprotective effect for liposomes in plasma stored at -20 °C, achieving about 90% entrapment efficiency, compared to about 60% in the control group without CPAs. Mechanistic investigations confirmed that CPAs protect liposomes against mechanical stress, prevent membrane disruption, and reduce ice damage by inhibiting recrystallization and adjusting bilayer hydration. These findings offer practical solutions for accurate pharmacokinetic assessments and reliable personalized dosing, safer alternative for liposomal drug research, biobanking, and real-world therapeutic monitoring.