Department of Organic Biomaterials , Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , 2-3-10 Kanda-Surugadai , Chiyoda , Tokyo 101-0062 , Japan.
Biomacromolecules. 2018 Jun 11;19(6):2238-2247. doi: 10.1021/acs.biomac.8b00301. Epub 2018 May 2.
In prior research it has been demonstrated that methylated β-cyclodextrins-threaded acid-labile polyrotaxanes (Me-PRXs) exhibit a lower critical solution temperature (LCST) and form coacervate droplets above their LCST. In this study, the encapsulation of proteins in coacervate droplets and the pH-responsive release of proteins, through the acid-induced dissociation of the Me-PRX, were investigated. The coacervate droplets encapsulate various proteins, such as bovine serum albumin (BSA), lysozyme, and β-galactosidase, at pH 7.4, into their hydrophobic inner phase. Concomitant with the pH-dependent dissociation of the Me-PRXs, the coacervates degraded below pH 6.5 and released encapsulated proteins, with the intrinsic activity of proteins maintained. Additionally, the subcutaneous injection of coacervate droplets encapsulating BSA in mice revealed that the retention time of the BSA at the injection site was prolonged compared to that of free BSA. Altogether, the coacervate droplets of the Me-PRX would be utilized as a new class of pH-responsive and injectable carrier for the controlled release of therapeutic proteins.
在先前的研究中已经证明，甲基化β-环糊精-穿线酸易失活聚轮烷（Me-PRX）在其低临界溶解温度（LCST）以上表现出较低的临界溶解温度（LCST），并形成凝聚液滴。在这项研究中，研究了凝聚液滴中蛋白质的包封以及蛋白质的 pH 响应释放，通过 Me-PRX 的酸诱导解离来实现。凝聚液滴在 pH 7.4 时将各种蛋白质（如牛血清白蛋白（BSA）、溶菌酶和β-半乳糖苷酶）包封到其疏水性内相中。与 Me-PRX 的 pH 依赖性解离同时发生，凝聚物在 pH 值低于 6.5 时降解并释放包封的蛋白质，同时保持蛋白质的固有活性。此外，将 BSA 包封在凝聚液滴中的 Me-PRX 的皮下注射在小鼠中表明，与游离 BSA 相比，BSA 在注射部位的保留时间延长。总的来说，Me-PRX 的凝聚液滴可用作一类新的 pH 响应和可注射载体，用于治疗性蛋白质的控制释放。
