PCFM Lab and GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
Department of Otorhinolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Carbohydr Polym. 2015 Sep 5;128:163-70. doi: 10.1016/j.carbpol.2015.04.024. Epub 2015 Apr 21.
A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by (1)H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.
一种前药胶凝策略被开发用于盐酸阿霉素（DOX·HCl）的持续和双重刺激-响应释放，盐酸阿霉素是一种常用的抗癌药物。为此，通过酸不稳定的腙键将 DOX·HCl 化学偶联到巯基化透明质酸（HA）上，并通过（1）H NMR 分析进行了验证。当暴露于空气中时，这种多糖缀合物在水溶液中表现出独特的自胶凝能力。胶凝时间和程度主要取决于巯基化 HA 上巯基的含量。所得水凝胶表现出主要的弹性响应和触变性。特别是，它可以以双重 pH 和还原响应模式持续释放共轭 DOX·HCl。在模拟癌细胞细胞内环境的条件下，发现累积药物释放明显加快。用各种释放介质处理的人鼻咽癌 CNE2 细胞的体外细胞毒性测定证实了这种缀合水凝胶对癌细胞抑制的有效性。
