{"title":"响应面法制备醋酸Leuprolide纳米颗粒及其优化:体外和离体评价。","authors":"Tosha Pandya, Abhay Dharamsi","doi":"10.1089/adt.2022.051","DOIUrl":null,"url":null,"abstract":"<p><p>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-<i>co</i>-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 <i>in vitro</i> drug release study, <i>ex vivo</i> 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 <i>in vitro</i> 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 <i>ex vivo</i> diffusion study indicated an apparent permeability coefficient of 5.0 + 0.3 × 10<sup>4</sup> for drug-containing NPs, which was higher than for plain drug solution (2.0 + 0.2 × 10<sup>4</sup>). 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.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preparation and Optimization of Leuprolide Acetate Nanoparticles Using Response Surface Methodology: <i>In Vitro</i> and <i>Ex Vivo</i> Evaluation.\",\"authors\":\"Tosha Pandya, Abhay Dharamsi\",\"doi\":\"10.1089/adt.2022.051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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-<i>co</i>-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 <i>in vitro</i> drug release study, <i>ex vivo</i> 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 <i>in vitro</i> 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 <i>ex vivo</i> diffusion study indicated an apparent permeability coefficient of 5.0 + 0.3 × 10<sup>4</sup> for drug-containing NPs, which was higher than for plain drug solution (2.0 + 0.2 × 10<sup>4</sup>). 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.</p>\",\"PeriodicalId\":8586,\"journal\":{\"name\":\"Assay and drug development technologies\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2022-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Assay and drug development technologies\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/adt.2022.051\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Assay and drug development technologies","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/adt.2022.051","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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.
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