Preparation and characterization of doxorubicin nanocarriers based on thermoresponsive oligo(ethylene glycol) methyl ether methacrylate polymer-drug conjugates

Aggregation of thermoresponsive chains to form mesoglobules is a promising way to make nanoaggregates useful as drug carriers. Here, we present for the first time, a route for the formulation of mesoglobules that may be used as polymer carriers for doxorubicin (DOX). For this purpose, a thermoresponsive terpolymer composed of diethylene glycol methyl methacrylate, oligoethylene glycol methyl methacrylate (300 g/mol), and 2-aminoethyl methacrylate hydrochloride was synthesized. Amino groups of polymers have been modified to azide or prop-2-yn-1-yl carbamate groups. Azide groups were used to conjugate modified DOX to polymer chains by the Huisgen cycloaddition reaction. The temperature aggregation of terpolymers, polymer-DOX conjugate and their mixtures was examined. Drug nanocarriers were formed by "click" crosslinking of thermally coaggregated mesoglobules of the conjugate and terpolymer with alkyne groups. Hydrolysable carbamate bonds allows for the nanoparticles disintegration and release of drug at various pH levels (5.5 and 7.4), with and without enzyme.