Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus
Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus
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基于 pH 响应性脂肪族聚碳酸酯的肠溶聚合物，经维生素 E 功能化，促进他克莫司的口服给药
DOI：
10.1021/bm501847u
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发表时间：
2015
影响因子：
6.2
通讯作者：
He Zhonggui
中科院分区：
文献类型：
--
作者：
Wang Menglin;Sun Jin;Zhai Yinglei;Lian He;Luo Cong;Li Lin;Du Yuqian;Zhang Dong;Ding Wenya;Qiu Shuhong;Liu Yuhai;Kou Longfa;Han Xiangfei;Xiang Rongwu;Wang Yongjun;He Zhonggui
为了提高口服药物的生物利用度，我们合成了一种ph敏感聚合物（聚（乙二醇）-聚（2-甲基-2-羧基-碳酸丙烯酯）-维生素E， mPEG-PCC-VE），试图将肠溶包衣和p -糖蛋白（P-gp）抑制的优点结合起来。脂族聚碳酸酯链通过聚合后改性被羧基和维生素E功能化。通过对比和中心复合设计优化，mpeg113 - pcc32 - ve4具有较低的临界胶束浓度（1.7 × 10-6mg /mL）和较高的他克莫司载药能力（21.2%±2.7%,w/w）。ph响应谱通过ph依赖性肿胀和体外药物释放来证实。模拟胃液作用2.5 h后，他克莫司释放量小于4.0%，而模拟肠液作用2.5 h后，他克莫司立即释放。mpeg113 - pcc32 - ve4胶束显著增加了P-gp底物他克莫司在全肠的吸收。大鼠口服他克莫司胶束的生物利用度比他克莫司溶液高6倍。因此，这种肠道聚合物有潜力成为一种有用的口服药物的纳米级载体。
To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)–poly(2-methyl-2-carboxyl-propylene carbonate)–vitamin E, mPEG–PCC–VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113–PCC32–VE4exhibited low critical micelle concentration of 1.7 × 10–6mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling andin vitrodrug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113–PCC32–VE4micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.