Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 52c, Josef Möller Haus, 6020 Innsbruck, Austria.
Drug Deliv. 2011 Aug;18(6):432-40. doi: 10.3109/10717544.2011.577108. Epub 2011 May 11.
It was the aim of this study to develop a nanoparticulate oral drug delivery system for leuprolide based on polyacrylic acid (PAA). In order to achieve formation of nanoparticles in a mild, aqueous environment, two different techniques were combined, namely hydrophobic ion pairing between leuprolide and sodium dodecyl sulphate in a first step, followed by encapsulation into nanoparticles gained by interpolymer complexation between polyacrylic acid and Pluronic F68. The obtained nanoparticles were characterized regarding particle size distribution, drug encapsulation efficiency and in vitro release profile. Additionally, the pharmacokinetic profiles of leuprolide after oral administration of PAA-nanoparticulate and PAA-control tablets to male Sprague-Dawley rats were assessed and compared. It could be shown, that hydrophobic ion pairing increased encapsulation efficacy of leuprolide and leads to a slowed drug release of nanoparticulate suspensions. Relative oral bioavailability of leuprolide could be increased by nanoparticulate tablets up to 4.2-fold. Results verify that the suggested approach is a promising strategy for the design of oral delivery systems for oral administration of peptide drugs.
本研究旨在基于聚丙烯酸 (PAA) 开发一种用于亮丙瑞林的纳米口服药物递送系统。为了在温和的水性环境中形成纳米颗粒，我们结合了两种不同的技术，即在第一步中使用亮丙瑞林和十二烷基硫酸钠之间的疏水离子配对，然后通过聚丙烯酸和泊洛沙姆 F68 之间的聚合物复合将其包封到纳米颗粒中。对所得纳米颗粒进行了粒径分布、药物包封效率和体外释放特性的表征。此外，还评估并比较了亮丙瑞林经雄性 Sprague-Dawley 大鼠口服 PAA-纳米颗粒和 PAA-对照片剂后的药代动力学特征。结果表明，疏水离子配对增加了亮丙瑞林的包封效率，并导致纳米颗粒混悬液的药物释放减缓。纳米颗粒片剂可使亮丙瑞林的相对口服生物利用度提高至 4.2 倍。这些结果验证了该方法是设计用于肽类药物口服给药的口服递送系统的一种有前途的策略。
