CAJ | 학술논문

利用肝素前体K5多糖，通过腙键（Hydrazone bond）连接抗肿瘤药物阿霉素（DOX），制备具有pH敏感性的K5-hydrazone-DOX（KHD）前体药物。对其载药量、形貌和体外药物释放等性质进行了研究，并通过HeLa细胞对其体外细胞毒性和细胞摄取进行了评价。结果表明，所制备的KHD前体药物中，DOX质量分数为18.0%。药物释放结果显示，KHD前体药物在pH 5.0条件下对DOX的释放率远高于pH 7.4条件下的释放率，具有明显的pH响应性。细胞实验表明， KHD前体药物可迅速被细胞摄取，并且具有肿瘤细胞抑制作用。本研究结果表明，KHD是一种有潜在应用价值的抗肿瘤前体药物。
이용간소전체K5다당，통과종건（Hydrazone bond）련접항종류약물아매소（DOX），제비구유pH민감성적K5-hydrazone-DOX（KHD）전체약물。대기재약량、형모화체외약물석방등성질진행료연구，병통과HeLa세포대기체외세포독성화세포섭취진행료평개。결과표명，소제비적KHD전체약물중，DOX질량분수위18.0%。약물석방결과현시，KHD전체약물재pH 5.0조건하대DOX적석방솔원고우pH 7.4조건하적석방솔，구유명현적pH향응성。세포실험표명， KHD전체약물가신속피세포섭취，병차구유종류세포억제작용。본연구결과표명，KHD시일충유잠재응용개치적항종류전체약물。
In this study, K5 polysaccharide (heparosan) was conjugated with anticancer drug DOX via hydrazone bond to obtain pH-sensitive K5-hydrazone-DOX (KHD) prodrug. The drug loaded capacity, morphology, and in vitro drug release were investigated. Its in vitro cytotoxicity and cellular uptake against HeLa cells were also evaluated. The results showed that the DOX content of KHD is 18.0%. The release rate of DOX at pH 5.0 was much faster than that at pH 7.4, revealing a pH-triggered release manner. The KHD prodrug could achieve intracellular delivery and showed effective cytotoxicity in vitro. This study indicates that the KHD prodrug may be a potential candidate for cancer therapy.