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  • Title: A pH-responsive prodrug delivery system self-assembled from acid-labile doxorubicin-conjugated amphiphilic pH-sensitive block copolymers.
    Author: Huang X, Liao W, Xie Z, Chen D, Zhang CY.
    Journal: Mater Sci Eng C Mater Biol Appl; 2018 Sep 01; 90():27-37. PubMed ID: 29853091.
    Abstract:
    The development of intelligent drug delivery system that can efficiently deliver doxorubicin (DOX) to tumor site with controlled drug release performance and enhanced therapeutic efficacy is of great significance for cancer chemotherapy. In this report, a nano-prodrug system was prepared successfully by conjugating DOX to pH-sensitive amphiphilic diblock copolymer poly (ethylene glycol) methyl ether‑b‑poly (β‑amino esters) through acid-labile cis‑aconityl moiety (mPEG-b-PAE-cis-DOX). The resultant complex copolymer-drug was able to self-assemble into polymeric micelles (PMs) in an aqueous solution at low concentration, and the critical micelle concentration (CMC) was 3.6 mg/L which was increased as decrease of pH value. H-nuclear magnetic resonance (1H NMR), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), transition electron microscopy (TEM), and classic acid-base titration were combined to confirm and characterize the chemical structure of the copolymer/drug conjugates and the physicochemical properties of the prodrug system. The DOX loading capacity, drug delivery and therapeutic efficacy of the conjugates were evaluated in vitro and in vivo. Notably, the antitumor experiments in tumor-bearing mice demonstrated that the pH-responsive nano-prodrug system effectively enhanced the therapeutic efficacy in comparison to free drug. All above results suggested that pH-responsive prodrug system has the potential to be effective carrier for the DOX delivery and pH-triggered controlled release.
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