Double-Hydrophilic Block Copolymers Based on Functional Poly(ε-caprolactone)s for pH-Dependent Controlled Drug Delivery

Abstract

The 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 (PEGb-PCL(NH 2 )), 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.

Multi‐Responsive Bottlebrush‐Like Unimolecules Self‐Assembled Nano‐Riceball for Synergistic Sono‐Chemotherapy

“…[ 1 ] However, extensively reported polymeric materials suffer from an undesirable high critical micellar concentration (CMC) value, a negatively correlated indicator of stability to drug pre‐leakage, even the CMC value of commercial PEG‐PCL and PLA‐PEG‐PLA carriers is almost over 49.6 µg mL −1 . [ 2 ] Furthermore, common linear PEGs‐based polymeric material short of coupling ability against drug molecules limits its drug loading capacity (DC) (mostly less than 10 wt%) [ 3 ] and bioavailability, which extremely affect therapeutic efficiency. Therefore, it is imperative to develop polymer carriers with high drug loading content and low CMC to surmount the obstacles.…”

Double hydrophilic block copolymers self-assemblies in biomedical applications

“…It is therefore our belief that the development of scale up friendly chemical strategies allowing for a rapid preparation of functional synthetic polymer blocks is one challenge to be tackled by the polymer community. Of notice, post-chemical modifications of selected polymer structures to generate macromolecular diversity appears to be highly attractive, especially with the use of "click chemistry" methodologies, that allow a rapid fine tuning of the polymers' structures [76,94,98,101,104].…”

“…Noteworthy, the morphology of the self-assemblies changed from spherical at pH 5 with a diameter of 65 nm to worm-like micelle upon pH increase to 8. Thanks to the carboxyl and the secondary amine groups, fluorescent molecules were attached to the copolymer to form stimuliresponsive fluorescent materials [100].Our group recently reported on a straightforward, 3-step synthetic strategy for the preparation of DHBCs with PCL blocks containing carboxylic acid, amine or hydroxyl functional moieties[101]. PEG-b-PCL copolymers were prepared via ROP of CL employing mPEG as macroinitiator, followed by post-polymerization functionalization of the PCL blocks with pendant alkyne groups using an anionic modification technique[102,103].…”

Effects of Polymer Block Length Asymmetry and Temperature on the Nanoscale Morphology of Thermoresponsive Double Hydrophilic Block Copolymers in Aqueous Solutions

“…Double hydrophilic block copolymers are of great interest as a subclass of stimuli-responsive materials with strong potential in many fields from efficient synthetic templates for engineering mineralization of inorganic crystalline materials to catalysis, nanoreactor engineering, supramolecular hydrogelation, and drug delivery , or ribonucleic acid complexation agents . Self-assembled structures from double hydrophilic block copolymers can result from hydrogen bond interactions and act as simplified synthetic analogues to the much more complex biomacromolecular assemblies and organelles in living cells .…”