Key Laboratory of Jiangxi University for Applied Chemistry and Chemical Biology, Yichun University, Yichun 336000, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China.
College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China.
Colloids Surf B Biointerfaces. 2023 Jun;226:113285. doi: 10.1016/j.colsurfb.2023.113285. Epub 2023 Mar 30.
Prodrug nanoassemblies fabricated by anticancer drug conjugates exhibited more advantages in controlled drug release and bioavailability and favorable antitumor efficacy. In this paper, lactobionic acid (LA) was connected with polyethylene glycol through amido linkages, and paclitaxel was joined with polyethylene glycol by means of ester bonds to form the prodrug copolymer LA-PEG-PTX. Then, LA-PEG-PTX was automatically assembled into LA-PEG-PTX nanoparticles (LPP NPs) by dialysis. The LPP NPs had a relatively uniform size of approximately 200 nm, a negative potential (-13.68 mV), and a spherical shape under TEM. The drug loading of LPP NPs was 3.91%, which was measured by HPLC. The in vitro release profile of LPP NPs exhibited a sustained release feature. The results of the pharmacokinetic test in rats showed that LPP NPs had higher T and AUC values than the control group (free PTX) and a prolonged in vivo circulation time, thus increasing the bioavailability of PTX. Remarkably, the LPP NPs were absorbed into HepG2 cells after galactose-directed internalization and enhanced cytotoxicity. Consequently, LPP NPs displayed notable antitumor activity in Kunming mice with H22 hepatocellular carcinoma. Collectively, these findings suggested that paclitaxel prodrug-based self-assembled nanoparticles were a promising alternative for improving the bioavailability and antitumor effect of PTX.
前药纳米组装体由抗癌药物偶联物制备，在控制药物释放和生物利用度以及良好的抗肿瘤疗效方面表现出更多优势。在本文中，通过酰胺键将乳糖酸（LA）与聚乙二醇连接，通过酯键将紫杉醇与聚乙二醇连接，形成前药共聚物 LA-PEG-PTX。然后，通过透析将 LA-PEG-PTX 自动组装成 LA-PEG-PTX 纳米颗粒（LPP NPs）。LPP NPs 的粒径约为 200nm，具有负电位（-13.68mV），TEM 下呈球形。通过 HPLC 测量，LPP NPs 的载药量为 3.91%。LPP NPs 的体外释放曲线表现出持续释放的特征。大鼠药代动力学试验结果表明，LPP NPs 的 T 和 AUC 值均高于对照组（游离 PTX），体内循环时间延长，从而提高了 PTX 的生物利用度。值得注意的是，LPP NPs 通过半乳糖介导的内化被吸收到 HepG2 细胞中，并增强了细胞毒性。因此，LPP NPs 在昆明小鼠 H22 肝癌模型中表现出显著的抗肿瘤活性。总之，这些发现表明，基于紫杉醇前药的自组装纳米颗粒是提高 PTX 生物利用度和抗肿瘤效果的一种有前途的选择。
