The Preparation And Characterization Of Anticancer Prodrug Based On Pendant Group Functionalized Amphiphilic Aliphalic Polyester

As a major class of biodegradable and biocompatible polymer, aliphatic polyesters have been widely used to prepare drug carrier, and conjugate with drug to improve the bioavailability. To achieve a high loading of polymer-drug conjugates(PDCs), functionalized polyesters with multiple reactive sites per chain must be prepared. Toxic catalyst shouldn’t be used during the synthesis of functional polyester and PDCs for the goal of hypotoxcity. Furthermore, the PDCs with environment responsive is highly preferred to minimized their side effect and to improve drug delivery efficiency.In this article, we synthesizsed functionalized polyester MPEG-b-PLA, MPEG-b-PαBrCL through ring-opening polymerization of the lactide and caprolactone monomer by using MPEG5000 as initiator. Utilizing the postpolymerization functionalization strategy, pendent aldehyde functionalized amphiphilic MPEG-b-PLA-g-aldehyde and pendent hydrazide functionalied MPEGb-P(CL-hyd) were prepared by the 1, 3-dipolar cycloaddition and thiol- bromine click reaction respectively.Meanwhile,we gained functionalized paclitaxels(HS-PTXL,LEV-PTXL) through esterification. Furthermore,we prepared a amphiphilic PDC loading PTXL(MPEG- b-(PLA-g-PTXL) by high efficiency and green thiol-click reaction and a pH sensitive PDC with hydrazone(MPEG-b-P(CL-hyd-LEV-PTXL)).With methoxy aniline as model drug, making it link with amphiphilic polylactide by imine bond,we prepared pH sensitive pro-drug. As revealed DLS and TEM, the amphiphilic PDCs assembled as micelle with the size 60~100 nm. MTT test of the polymers and pro-drugs suggested that the polymers have excellent biological compatibility and have able to act as drug-loading materials to A549、 MCF-7cell lines,and the pro-drugs have favourable anticancer activity within the range of the 0.1~10 μg/m L drug concentration. The drug release behavior of simulation pro-drug in vitro shows that simulation pro-drug keeps stable under physiological pH, and labile under the pH of tumor tissues.We have prepared the functionalized amphiphilic block polymer, PDCs, and self-assembled micelles. The functionalized polymers contain multiple reactive sites, resulting in high efficiency of drug loading. Moreover,the synthesis of polymer and pro-drug haven’t brought in any toxic catalyst, the MTT result has proved its anticancer efficiency, as a conclusion, a pro-drug with high efficiency of drug loading and low side effect has been prepared.