Ph. D. Program for Biotech Pharmaceutical Industry, School of Pharmacy, China Medical University, Taichung 404, Taiwan.
Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan.
Int J Mol Sci. 2018 Nov 17;19(11):3625. doi: 10.3390/ijms19113625.
Curcumin has been proven to be a potent agent in colon cancer treatment. However, its hydrophobicity and low oral bioavailability hampered its clinical application. These limitations could be improved through appropriate formulations such as using polyelectrolyte complexes (PECs). PECs were self-assembled with polycations and polyanions in polar solvents. In this study, a novel pectin-type B gelatin PEC was developed for use in curcumin formulation. At pH 4.0, natural polyanions pectin and polycations type B gelatin spontaneously formed PECs in ethanol/water solution, whereas under mimetic gastrointestinal tract (GI tract) conditions, at pH 2.0 and 8.0, pectin and type B gelatin were electrically neutralized, and the PECs swelled to allow payload release. After being transferred to pH 7.0 condition, as in the colon environment, PECs were internalized into colon carcinomas. Thus, pectin-type B gelatin PECs were successfully prepared, and their constituent ratio and drug-loading process were also optimized. The optimum particle size of the PECs was 264.0 ± 3.1 nm and they could swell as the zeta potential was altered at either pH 2.0 or 8.0. The optimum drug content and loading efficiency were 40% and 53%, respectively. At pH 2.0, curcumin was rapidly released from curcumin-loaded PECs, whereas at pH 8.0, curcumin-loaded PECs showed a sustained-release of curcumin. The bare PECs showed very low toxicity toward human normal cells, whereas curcumin-loaded PECs, after incubation at pH 2.0 for 2 h and at pH 8.0 for 4 h, induced cell cycle arrest and exhibited cytotoxic effect to HCT116 human colon cancer cells, even though these loaded PECs were pretreated with mimetic GI tract conditions. Our pectin-type B gelatin PECs were shown to be a promising oral formulation for curcumin delivery in anticancer therapy.
姜黄素已被证明是治疗结肠癌的有效药物。然而，其疏水性和低口服生物利用度限制了其临床应用。这些局限性可以通过适当的制剂来改善，例如使用聚电解质复合物（PEC）。PEC 是在极性溶剂中由聚阳离子和聚阴离子自组装形成的。在这项研究中，开发了一种新型果胶型 B 明胶 PEC 用于姜黄素制剂。在 pH4.0 时，天然聚阴离子果胶和聚阳离子 B 型明胶在乙醇/水溶液中自发形成 PEC，而在模拟胃肠道（GI 道）条件下，在 pH2.0 和 8.0 时，果胶和 B 型明胶被电中和，PEC 膨胀以允许payload 释放。当转移到 pH7.0 条件下时，例如在结肠环境中，PEC 被内化到结肠癌细胞中。因此，成功制备了果胶型 B 明胶 PEC，并对其组成比例和载药过程进行了优化。PEC 的最佳粒径为 264.0±3.1nm，当 pH2.0 或 8.0 时，其粒径可以通过改变zeta 电位来膨胀。最佳药物含量和载药量分别为 40%和 53%。在 pH2.0 时，姜黄素从载姜黄素 PEC 中迅速释放，而在 pH8.0 时，载姜黄素 PEC 表现出姜黄素的持续释放。裸 PEC 对人正常细胞的毒性非常低，而载姜黄素 PEC 在 pH2.0 孵育 2 小时和 pH8.0 孵育 4 小时后，诱导细胞周期停滞，并对 HCT116 人结肠癌细胞表现出细胞毒性作用，即使这些载药 PEC 经过模拟胃肠道条件预处理。我们的果胶型 B 明胶 PEC 有望成为一种有前途的口服制剂，用于姜黄素在抗癌治疗中的传递。
