Zhang Xingwang, Chen Guijiang, Zhang Tianpeng, Ma Zhiguo, Wu Baojian
Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2014 Nov 26;9:5503-14. doi: 10.2147/IJN.S73340. eCollection 2014.
Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl(®)), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.
脂质纳米载体正成为亲脂性药物口服给药的通用平台。在本文中，我们旨在探究脂质纳米颗粒的胃肠道行为以及聚乙二醇化对非诺贝特（一种生物药剂学分类系统（BCS）II类模型药物）口服吸收的影响。通过溶剂扩散法制备了负载非诺贝特的聚乙二醇化脂质纳米颗粒（FN-PLN），并通过粒径分布、形态、傅里叶变换红外光谱和药物释放对其进行了表征。进行了脂解实验以评估脂质纳米颗粒对胰脂肪酶的抗性。在大鼠口服给予FN制剂后评估其药代动力学。所制备的FN-PLN粒径为186.7 nm，包封率>95%。与传统脂质纳米颗粒相比，PLN在含脂肪酶的介质中药物释放较慢，粘蛋白结合显著减少，并且在体外脂解受到抑制。此外，使用PLN可显著增强FN的口服吸收，相对于传统脂质纳米颗粒和市售制剂（力平之（®）），其相对生物利用度分别为123.9%和157.0%。结果表明，粘蛋白捕获减少、脂解抑制和/或粘膜通透性改善是口服吸收增加的原因。这些结果有助于更好地理解脂质纳米颗粒在体内的命运，并表明PLN作为BCS II类药物口服载体的潜力。
