An Intestinal "Transformers"-like Nanocarrier System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs
An Intestinal "Transformers"-like Nanocarrier System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs
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DOI：
10.1021/acsnano.8b00470
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发表时间：
2018-07-01
期刊：
影响因子：
17.1
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
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作者：
Chuang, Er-Yuan;Lin, Kun-Ju;Sung, Hsing-Wen
长期以来，将口服给药的水溶性差的药物（其口服生物利用度差）的肠溶出增加到治疗有效水平一直是一个难以实现的目标。在这项工作中，开发了一种方法，可以大大提高水溶性差的药物，如姜黄素（CUR）的口服生物利用度，使用“变形金刚”样的纳米载体系统（TLNS），可以在肠腔中自我包裹药物分子，形成纳米乳液。由于其已知的抗炎活性，本文评价了CUR在治疗胰腺炎中的用途。在体外证实了TLNS在肠环境中形成负载CUR-loaded纳米乳剂的结构变化。在实验诱导的急性胰腺炎（AP）大鼠中评价该TLNS的治疗功效。值得注意的是，使用所提出的TLNS获得的负载CUR-loaded纳米乳剂可以被动靶向肠M细胞，其中它们被转胞吞，然后通过肠淋巴系统转运到胰腺组织中。用TLNS处理的大鼠胰腺产生比接受游离CUR的对应物强约12倍的CUR信号，潜在地改善AP的恢复。这些发现表明，所提出的TLNS可以显着增加肠道药物溶出，使口服给药的水溶性差的药物的有利的非侵入性手段。
Increasing the intestinal dissolution of orally administered poorly water-soluble drugs that have poor oral bioavailability to a therapeutically effective level has long been an elusive goal. In this work, an approach that can greatly enhance the oral bioavailability of a poorly watersoluble drug such as curcumin (CUR) is developed, using a "Transformers"-like nanocarrier system (TLNS) that can self-emulsify the drug molecules in the intestinal lumen to form nanoemulsions. Owing to its known anti-inflammation activity, the use of CUR in treating pancreatitis is evaluated herein. Structural changes of the TLNS in the intestinal environment to form the CUR-laden nanoemulsions are confirmed in vitro. The therapeutic efficacy of this TLNS is evaluated in rats with experimentally induced acute pancreatitis (AP). Notably, the CUR-laden nanoemulsions that are obtained using the proposed TLNS can passively target intestinal M cells, in which they are transcytosed and then transported into the pancreatic tissues via the intestinal lymphatic system. The pancreases in rats that are treated with the TLNS yield approximately 12 times stronger CUR signals than their counterparts receiving free CUR, potentially improving the recovery of AP. These findings demonstrate that the proposed TLNS can markedly increase the intestinal drug dissolution, making oral delivery a favorable noninvasive means of administering poorly water-soluble drugs.