Synthesis of pH-sensitive, water-soluble paclitaxel prodrugs based on norbornene-functional polylactide by copper-free click chemistry

Abstract

2016) Synthesis of pH-sensitive, water-soluble paclitaxel prodrugs based on norbornene-functional polylactide by copper-free click chemistry, International Journal of Polymeric Materials and Polymeric Biomaterials, 65:15,[789][790][791][792][793][794][795][796] ABSTRACT In this study, a novel polymeric prodrug based on norbornene-functional polylactide with functionalized paclitaxels (LEV-PTXL) covalently conjugated to water-soluble polymer carrier via a pH-sensitive hydrazone bond was developed. A series of water-soluble PTXL prodrugs with decent drug contents of 17.3 and 24.7 wt% (denoted as PTXL prodrugs 1 and 2) were prepared. The molecular structures and characteristics were confirmed by 1 H NMR, Fourier transform infrared, and gel permeation chromatography. In vitro release studies showed that PTXL release rate from polymeric prodrug were significantly accelerated under acidic medium, due to the acid-cleavable hydrazone linkage. As illustrated by cytotoxicity study, while the corresponding polymer carrier was nontoxic, the polymeric prodrug exhibited higher therapeutic efficacy toward MCF-7 and A549 (IC50 ¼ 0.19 and 4.94 µg PTXL equiv/mL, respectively) cancer cells. The norbornene-functional polylactide-based polymeric prodrug has appeared as a novel anticancer nanomedicine for cancer therapy. GRAPHICAL ABSTRACT ARTICLE HISTORY