Preparation, physicochemical characterization, ex vivo, and in vivo evaluations of asiatic acid-loaded solid lipid nanoparticles formulated with natural waxes for nose-to-brain delivery

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2024-10-15 DOI:10.1016/j.ejps.2024.106935

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Abstract

Asiatic acid (AA) has neuroprotective potential for prevention and treatment of Alzheimer's disease. Natural waxes with various ratios of Tween 80 and Span 80 or soybean lecithin were formulated to obtain AA-loaded solid lipid nanoparticles (AA-SLN) to improve direct nose to brain transport. Optimal AA-SLN had particle size below 200 nm with uniform size distribution and zeta potential of nearly -30 mV indicating a low risk of particle aggregation. Formulation with rice bran wax, Tween 80, and soybean lecithin (AA-RwS₁₀₀) showed the highest entrapment efficiency and yield of >98 % while in vitro AA release of AA-SLN was linearly up to 48 h For ex vivo permeation, confocal laser scanning microscopy (CLSM) and histopathological studies on porcine olfactory mucosa (OM) and respiratory mucosa (RM), AA-SLN showed significantly higher permeation across OM than RM (p < 0.05) up to 6 h and AA-RwS100 also showed the highest amount of drug permeated as confirmed by CLSM results. Although AA-SLN showed non-significantly lower permeation than AA solution (AA-SOL) (p > 0.05), no epithelial and mucosal structure damages were observed in OM treated with AA-RwS₁₀₀ and RM treated with all AA-SLNs indicating safety for nasal administration while AA-SOL showed significant damage to both OM and RM. In addition, in vivo brain distribution study by fluorescence imaging using Rhodamine (R6g) showed higher brain distribution after intranasal administration of R6g-loaded solid lipid nanoparticles (R6g-SLN) than R6g solution (R6g-SOL) and intravenous administration of R6g-SLN, and R6g-RwS₁₀₀ also showed the highest brain accumulation at 8 h post administration.

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用于鼻脑给药的天然蜡配制的积雪草酸固体脂质纳米颗粒的制备、理化表征、体内外评价

积雪草酸（AA）具有预防和治疗阿尔茨海默病的神经保护潜力。研究人员将天然蜡与不同比例的 Tween 80 和 Span 80 或大豆卵磷脂配制成 AA 负载固体脂质纳米颗粒（AA-SLN），以改善从鼻腔到大脑的直接运输。最佳 AA-SLN 的粒径低于 200 nm，粒度分布均匀，zeta 电位接近 -30 mV，表明颗粒聚集的风险较低。用米糠蜡、吐温 80 和大豆卵磷脂配制的配方（AA-RwS100）显示出最高的包埋效率和产量（>98 %），AA-SLN 的体外 AA 释放量在 48 小时内呈线性增长。在猪嗅粘膜（OM）和呼吸粘膜（RM）的体内渗透、共聚焦激光扫描显微镜（CLSM）和组织病理学研究中，AA-SLN 在 OM 中的渗透率明显高于 RM（p < 0.05），而且经 CLSM 结果证实，AA-RwS100 也显示出最高的药物渗透量。虽然 AA-SLN 的渗透率显著低于 AA 溶液（AA-SOL）（p > 0.05），但在用 AA-RwS100 处理的 OM 和用所有 AA-SLN 处理的 RM 中均未观察到上皮和粘膜结构损伤，这表明鼻腔给药是安全的，而 AA-SOL 则对 OM 和 RM 均有显著损伤。此外，通过使用罗丹明（R6g）进行荧光成像进行的体内脑分布研究表明，鼻内给药负载 R6g 的固体脂质纳米颗粒（R6g-SLN）的脑分布高于 R6g 溶液（R6g-SOL）和静脉给药 R6g-SLN，R6g-RwS100 在给药后 8 小时的脑累积量也最高。

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来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.