Pharmaceutical cocrystals prepared with a cucurbit[8]uril framework for intestine-targeted drug delivery
Pharmaceutical cocrystals prepared with a cucurbit[8]uril framework for intestine-targeted drug delivery
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DOI：
10.25177/jfst.4.3.ra.509
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发表时间：
2019-05
期刊：
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通讯作者：
Li-li Xu;Jing Jia;Kan Li;Hui Xu;Bin Di;Chi Hu;and Li-li Xu;Sift Desk Journals Open Access Journals-Sift-Desk-Journals-Open-Access-Journals-152222321
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文献类型：
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作者：
Li-li Xu;Jing Jia;Kan Li;Hui Xu;Bin Di;Chi Hu;and Li-li Xu;Sift Desk Journals Open Access Journals-Sift-Desk-Journals-Open-Access-Journals-152222321
将活性药物成分（api）封装在载体材料中，以便在所需部位进行受控递送，这对于优化治疗药物的有效性同时最小化其副作用至关重要。本文将Cucurbit[8]uril （CB[8]）组装为寄主框架，在室温下将原料药（色氨酸、苯丙氨酸双阿培南、双氯芬酸钠）置于水溶液中，增强其在胃酸中的稳定性，实现在肠道中的缓释。通过紫外-可见光谱研究了主-客体相互作用，通过单晶x射线分析确定了超分子组装体的晶体结构，结果表明CB[8]框架晶体和API@CB[8]共晶均属于单斜晶系。由于它们的芳香环折叠在CB[8]的大环腔内，它们的烷基链向外伸展，通过离子偶极相互作用和氢键与CB[8]的羰基入口相互作用，因此水系和疏水性原料药都很容易被封装在超分子框架内。与自由形式的原料药相比，在肠道pH值（6.8）下观察到API@CB[8]共晶的加速溶解动力学，而在胃pH值（1.5）下则显示出较低的溶解谱。细胞毒性试验证实了该药物共晶的生物相容性，为肠道靶向给药提供了新的范例。
Encapsulation of active pharmaceutical ingredients (APIs) in carrier materials for controlled delivery in the desired site is of paramount importance for optimizing the effectiveness of a therapeutic drug while minimizing its side effects. Cucurbit[8]uril (CB[8]) is herein assembled as a host framework to accommodate APIs (tryptophan, phenylalanine biapenem, and diclofenac sodium) in aqueous solution under room temperature to enhance their stability in the gastric acid and realize sustained release in the intestinal tract. Host-guest interactions were investigated by UV-vis spectroscopy while crystal structures of the supramolecular assembly were determined by single-crystal x-ray analysis, which reveals that both the CB[8] framework crystals and the API@CB[8] cocrystals belong to a monoclinic crystal system. With their aromatic rings folded inside the macrocyclic cavity of CB[8] and their alkyl chains stretching outside to interreact with the carbonyl portals of CB [8] through ion-dipole interactions and hydrogen bonding, both hydrophic and hydrophobic APIs were readily encapsulated inside the supramolecular framework. In comparison to API in its free form, an accelerated dissolution kinetic of the API@CB[8] cocrystals was observed at intestinal pH (6.8), which otherwise demonstrated a lower dissolution profile at gastric pH (1.5). With their biocompatibility confirmed by cytotoxicity test, the proposed pharmaceutical cocrystals provide a new paradigm for intestine-targeted drug delivery.