# Degradable Ureido‐Polycarbonate Block Copolymers with a Complex UCST Thermoresponse

## TL;DR

This paper introduces degradable block copolymers that self-assemble into micelles in water and show a unique temperature response, making them promising for drug delivery.

## Contribution

The study presents a new class of degradable, UCST-responsive block copolymers with potential for thermoresponsive drug delivery.

## Key findings

- The copolymers self-assemble into stable micelles in water and exhibit UCST-type thermoresponse.
- Increasing ureido group density enhances the UCST behavior of homopolycarbonates.
- The self-assemblies show potential as nanocarriers for hydrophobic drugs like curcumin.

## Abstract

In this work, amphiphilic block copolymers (BCs) consisting of a hydrophilic poly(ethylene glycol) methyl ether (PEG) and a degradable polycarbonate block derived from 2,2‐bis(hydroxymethyl)propionic acid (bis‐MPA) with pendant ureido units, along with corresponding homopolycarbonates are described. Polymers are synthesized by combining ring opening polymerization (ROP) and thiol‐ene/yne functionalization to incorporate UCST‐promoting ureido groups. For homopolycarbonates, increasing the ureido groups density along the polymer chain facilitates the upper critical solution temperature (UCST)‐type thermoresponse in water. Because of their amphiphilic character, BCs form stable self‐assemblies either by direct dispersion in water, co‐solvent method or microfluidics. Upon heating, these self‐assemblies swell, and collapse due to extensive hydration of the polycarbonate block, rather than becoming solubilized. Thermoresponsiveness is analyzed in terms of the number of ureido groups in the polycarbonate for a given polycarbonate block length as well as the length of polycarbonate block. As a proof of concept, the potential of these self‐assemblies as thermoresponsive drug nanocarriers is evaluated, using curcumin as a hydrophobic model drug.

Amphiphilic block copolymers with degradable ureido‐functionalized polycarbonate segments self‐assemble into spherical micelles in water, exhibiting an intriguing upper critical solution temperature (UCST) behavior. Upon heating, these micelles swell, collapse, and reorganize into highly hydrated condensates that mimic polymeric nanogels. Their potential as temperature‐responsive nanocarriers for hydrophobic drugs is demonstrated using curcumin as a drug model.