開發漆黃素聚乳酸甘醇酸奈米粒子及口服吸收效率評估

Development and oral absorption efficiency evaluation of fisetin-loaded poly (lactide-co-glycolide) nanoparticles

林佳禛(Chia-Chen Lin)

指導教授 ： 吳育澤

高雄醫學大學/藥學院/藥學系碩士班/碩士(2020年)

摘要

本研究利用奈米沉澱法製備漆黃素聚乳酸甘醇酸(poly (lactide-co-glycolide), PLGA)奈米粒子，以改善漆黃素的溶離速率與腸道吸收效率。研究中使用中央複合設計-反應曲面法進行配方優化，探討變因聚乙烯醇(poly (vinyl alcohol), PVA)濃度(X1)與聚乳酸甘醇酸(PLGA)的添加量(X2)跟漆黃素PLGA奈米粒子的粒徑(Y1)、包埋率(Y2)、界面電位(Y3)及分散係數(Y4)之間的關係。本研究評估漆黃素PLGA奈米粒子在pH 1.2、pH 6.8及pH 7.4溶液中的釋出情形，使用傅立葉轉換紅外光譜儀、高溫示差掃描熱分析法及X光粉末繞射儀探討漆黃素和PLGA之間的交互作用，透過翻腸試驗評估穿透性，以及進行60天安定性試驗。製備時使用0.5%(w/v) PVA溶液，添加5 mg漆黃素及75.3 mg PLGA為最佳配方。優化後的漆黃素PLGA奈米粒子其粒徑為187.9±6.1 nm、包埋率79.3±2.7%、界面電位-29.15±1.6 mV，以及分散係數0.121±0.01，漆黃素單位含量為0.05 g/g。在體外釋放試驗中，漆黃素PLGA奈米粒子相較於未製備成劑型的漆黃素，能夠有效提升溶離速率至少3倍。在穿透性評估試驗中，漆黃素PLGA奈米粒子相較於漆黃素懸浮液，在十二指腸的吸收提升4.9倍，空腸的吸收提升3.2倍，迴腸的吸收提升2.3倍。

關鍵字

漆黃素 ； 聚乳酸甘醇酸 ； 奈米粒子 ； 中央複合設計-反應曲面法

並列摘要

The purpose of the study was to prepare the fisetin-loaded poly (lactide-co-glycolide) (PLGA) nanoparticles by nanoprecipitation method to improve the dissolution rate and intestinal absorption efficiency of fisetin. The central composite design-response surface method (CCD-RSM) was employed to optimize the formulation and investigate the effects of poly (vinyl alcohol) (PVA) concentration (X1) and PLGA amount (X2) on the particle size (Y1), encapsulation efficiency (Y2), zeta potential (Y3) and polydispersity index (Y4). In vitro release was evaluated in pH 1.2, pH 6.8 and pH 7.4 dissolution medium. Interaction among fisetin and PLGA was studied by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis. Everted gut sac model was used to evaluate permeability. Stability studies were carried out for 60 days. The optimized formula is 0.5%(w/v) PVA solution, 5 mg fisetin, and 75.3 mg PLGA. The particle size, encapsulation efficiency, zeta potential, polydispersity index and fisetin drug content of the optimized formulation was 187.9±6.1 nm, 79.3±2.7%, -29.15±1.6 mV, 0.121±0.01, and 0.05 g/g, respectively. In the in vitro release test, fisetin-loaded PLGA nanoparticles can effectively increase the dissolution rate of fisetin compared to fisetin alone. In the permeability test, the absorption of fisetin-loaded PLGA nanoparticles increased 4.9-fold in the duodenum, 3.2-fold in the jejunum, and 2.3-fold in the ileum compared to fisetin suspension.

並列關鍵字

fisetin ； poly (lactide-co-glycolide) ； nanoparticle ； central composite design-response surface method

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