bm9b01006_si_001.pdf (432.01 kB)
Double-Hydrophilic Block Copolymers Based on Functional Poly(ε-caprolactone)s for pH-Dependent Controlled Drug Delivery
journal contribution
posted on 2019-10-16, 19:21 authored by Ayman El Jundi, Sytze Buwalda, Audrey Bethry, Sylvie Hunger, Jean Coudane, Youssef Bakkour, Benjamin NotteletThe
use of double-hydrophilic block copolymers (DHBCs) in biomedical
applications is limited by their lack of degradability. This additional
functionality has been obtained in the past through multistep chemical
strategies associated with low yields. In this work, a series of DHBCs
composed of a bioeliminable poly(ethylene glycol) (PEG) block and
hydrolyzable functional poly(ε-caprolactone) (PCL) blocks bearing
carboxylic (PEG-b-PCL(COOH)), amino (PEG-b-PCL(NH2)), or hydroxyl side groups (PEG-b-PCL(OH)) is synthesized in only three steps. DHBCs with
50% substitution degree with respect to the CL units are obtained
for all functional groups. The pH-dependent self-assembly behavior
of the DHBCs is studied showing critical micelle concentration (CMC)
variations by a factor of 2 upon pH changes and micellar mean diameter
variations of 20–30%. The potential of these partly degradable
DHBCs as drug-loaded polyion complex micelles is further exemplified
with the PEG-b-PCL(COOH) series that is associated
with the positively charged anticancer drug doxorubicin (DOX). Encapsulation
efficiencies, drug loadings, pH-controlled release, and cytotoxicity
of the DOX-loaded micelles toward cancer cells are demonstrated. This
set of data confirms the interest of the proposed straightforward
chemical strategy to generate fully bioeliminable and partly degradable
DHBCs with potential as pH-responsive drug-delivery systems.