Chylomicron-mimicked Bio-self-assembling MSNs to improve bioavailability of Oral Drugs via Promoting Lymphatic Transport
作者单位：Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University
会议名称：《2018年第十二届中国药物制剂大会》
会议日期：2018年
学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床]
关 键 词：lymphatic transport antiretroviral therapy oral bioavailability first-pass metabolism lymphatic target mesoporous silica nanocarrier lopinavir
摘 要：Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and reservation drugs at lymphatic tissues against lymphmediated diseases. This drug absorption pathway plays a win-win role in both pharmacokinetics and pharmacodynamics for antiretroviral therapy to fully suppress HIV. Herein, with the inspiration of triglyceride digestion process in the daily diet, we engineered a triglyceride-mimicked mesoporous silica nanocarrier（namely TMCMS） to promote lymphatic transport of antiretroviral drugs. Taking lopinavir（LNV） as a model antiretroviral drug with hurdles of poor solubility, high first pass effect and off-target disposition, TMCMS vector exhibited several properties belonging to ideal nanocarriers of high drug load, amorphous dispersion and controlled release in gastrointestinal tract, and also a perfect hydrolysis performance similar to TG pre-uptake. Subsequently, TMCMS showed a serious of TG-mimetic transport features across intestinal epithelial cells: hydrolysis–re-esterification–chylomicron assembly, participating into such a biochemical process and self-assembling to a chylomicron-associated TMCMS（namely TMCMS@CM） in enterocytes. As a result, TMCMS brought 10.6 folds oral bioavailability through circumventing first-pass metabolism through lymphatic transport pathway. Our study provides evidences of using the bio-selfassembling TMCMS nanocarrier to facilitate bioavailability and efficacy via lymphatic transport of oral drugs.