响应面法制备醋酸Leuprolide纳米颗粒及其优化:体外和离体评价。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Tosha Pandya, Abhay Dharamsi
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引用次数: 0

摘要

本研究旨在开发优化的醋酸leuprolide (LA)纳米颗粒(NPs),用于鼻内给药治疗阿尔茨海默病。采用Box-Behnken设计优化LA聚乳酸-羟基乙酸(PLGA) NPs。选取的自变量为PLGA浓度、表面活性剂浓度和水油比,因变量为粒径和%捕集效率。通过体外药物释放研究、体外扩散研究、组织病理学研究、溶血稳定性研究和模拟鼻液(SNF)稳定性评价优化后的NPs。优化后的纳米粒子粒径为182.6±1.5 nm,多分散性指数为0.3,包封率为77.3±0.6,zeta电位为-5.6 mv±0.2。体外释药率6 h为纯药释药率96%,48 h释药率仅为66.35%。体外扩散实验表明,含药NPs的表观通透系数为5.0 + 0.3 × 104,高于普通药液(2.0 + 0.2 × 104)。绵羊鼻毒性和溶血试验证明了该制剂的安全性。优化后的NPs在SNF中是稳定的。因此,通过设计方法从质量方面对LA纳米粒配方进行了优化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preparation and Optimization of Leuprolide Acetate Nanoparticles Using Response Surface Methodology: In Vitro and Ex Vivo Evaluation.

This study aims to develop optimized leuprolide acetate (LA) nanoparticles (NPs) for intranasal delivery in the treatment of Alzheimer's disease. Box-Behnken Design was used to optimize LA polylactide-co-glycolic acid (PLGA) NPs. The independent variables chosen were PLGA concentration, surfactant concentration, and the ratio of water to oil phase, whereas the dependent variables were particle size and % entrapment efficiency. The optimized NPs were evaluated by in vitro drug release study, ex vivo diffusion study, histopathology study, hemolytic stability study, and stability in simulated nasal fluid (SNF). The optimized NPs had particle size of 182.6 ± 1.5 nm, polydispersity index (0.3), % entrapment efficiency (77.3 ± 0.6), and zeta potential (-5.6 mv ±0.2). The in vitro drug release indicated 96% of pure drug release in 6 h, whereas only 66.35% of the drug was released from the optimized formulation at 48 h. The ex vivo diffusion study indicated an apparent permeability coefficient of 5.0 + 0.3 × 104 for drug-containing NPs, which was higher than for plain drug solution (2.0 + 0.2 × 104). Sheep nasal toxicity and hemolytic study proved the safety of formulation. The optimized NPs were found to be stable in SNF. Thus, nanoparticulate formulation of LA was optimized by quality by design approach.

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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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