Enteric complex layer-coated controlled release of capsaicin from phytosterol/γ-cyclodextrin microparticles via guest exchange reaction with taurocholic acid
Enteric complex layer-coated controlled release of capsaicin from phytosterol/γ-cyclodextrin microparticles via guest exchange reaction with taurocholic acid
复制标题
肠溶复合物层包衣通过与牛磺胆酸的客体交换反应从植物甾醇/γ-环糊精微粒中控制释放辣椒素
DOI：
10.1016/j.ejps.2021.106038
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发表时间：
2022
影响因子：
4.6
通讯作者：
Moribe Kunikazu
中科院分区：
文献类型：
--
作者：
Sasako Hiroshi;Koyama Kazuo;Higashi Kenjirou;Ueda Keisuke;Ishimoto Arisa;Moribe Kunikazu
植物甾醇(Pse)/γ-环糊精(γ-CD)微球具有胶囊状结构，其中疏水的PSE核心被亲水性PSE/γ-CD包合物晶体的外层包围。通过将辣椒素(CAP)包裹到微粒中，可以掩盖辣椒素(CAP)的不良味道。本文采用划桨法考察了PSE/γ-CD微球在人工肠液中的溶出度。PH为1.2和5.0时，微球中CAP的溶出度受到抑制。而在禁食和喂食状态下，模拟肠液(FaSSIF和FeSSIF)的溶出度显著增加。这些人工流体中含有牛磺胆酸盐(TCA)，导致CAP从微粒中迅速溶解。用环境1H核磁共振波谱研究了在TCA存在下，CAP从微粒中溶解的机理。在微粒与三氯乙酸混合悬浮液的孵育过程中，γ-CD峰开始出现，三氯乙酸的峰逐渐前移。核磁共振定量分析结果表明，三氯乙酸通过与γ的客体交换反应使γ-CD从微粒中溶解出来，从而在孵育过程中形成了包合物。PSE/γ-CD包合物晶体在微球外壳的崩塌可触发CAP进入肠液。因此，Pse/γ-CD微球可以作为肠内控释系统，通过与三氯乙酸的客体交换反应，而不是通过常规的pH变化来释放包囊药物。
Phytosterol (PSE)/γ-cyclodextrin (γ-CD) microparticles have a capsule-like structure, wherein the hydrophobic PSE core is surrounded by outer layers of the hydrophilic PSE/γ-CD inclusion complex crystal. The microparticles could mask the undesirable taste of capsaicin (CAP) by encapsulation of CAP into the microparticles. In the present study, the dissolution of CAP from PSE/γ-CD microparticles into artificial intestinal fluids was examined using the paddle method. The dissolution of CAP from the microparticles was suppressed at pH 1.2 and 5.0. On the other hand, the dissolution was significantly enhanced in fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF) . Taurocholate (TCA), contained in these artificial fluids, induced rapid dissolution of CAP from microparticles. The mechanism of CAP dissolution from the microparticles in the presence of TCA was investigated usingin situ1H NMR spectroscopy. During the incubation of the mixed suspension of the microparticles and TCA, γ-CD peaks started to appear, and the TCA peak showed a gradual upfield shift. Quantitative analysis of NMR results showed that the TCA/γ-CD inclusion complex could form during incubation, according to the dissolution of γ-CD from the microparticles via the guest exchange reaction of PSE by TCA. The collapse of the PSE/γ-CD inclusion complex crystal at the outer shell of microparticles could trigger the release of CAP into the intestinal fluid. Thus, PSE/γ-CD microparticles can be used as an enteric controlled-release system that releases encapsulated drugs not via the conventional pH changes but via guest exchange reaction with TCA.