Hyperbranched polyglycerol grafted poly(N,N-diethylacrylamide) thermoresponsive copolymers as biocompatible, highly efficient encapsulation and sustained release systems of curcumin

Abstract

Due to solubilization, encapsulation, stability and delivery difficulties of various drugs and drug candidates, investigating polymeric nanoparticles for drug delivery formulations is an extremely vital and challenging task. The ideal polymers should have biocompatibility, controlled drug uptake/release properties and colloidal stability over a wide temperature range. In this study, we propose poly(N,N-diethylacrylamide)-g-(hyperbranched polyglycerol) (PDEAAm-g-HbPG) thermoresponsive graft copolymers as candidates for drug formulations satisfying all the above-mentioned requirements. The PDEAAm-g-HbPG copolymers were synthesized by grafting amino-monofunctional HbPG onto PDEAAm chains containing pendant succinimide active ester groups. It has been found that the PDEAAm-g-HbPG graft copolymers are non-toxic to human monocytic cells, and do not cause haemolysis of human red blood cells. Furthermore, these grafts possess temperature-dependent reversible aggregation-disaggregation, i.e. thermoresponsive transitions, in water and PBS. The specific nanoassembling architecture of the copolymers resulted in enhanced encapsulation of curcumin with high drug loading content exceeding 25 % at 37 °C. The hydrophilic HbPG side chains provide high colloidal stability for the formulated drug dispersions from room temperature up to 45 °C as well as sustained release of curcumin. Formulating curcumin with these novel graft copolymers significantly enhanced its anticancer activity against HT-29 colorectal adenocarcinoma cells and the cell internalization of the drug. These properties of PDEAAm-g-HbPG copolymers make them superior compared to other hydrophilically modified polymer carriers indicating their great potential as advanced drug delivery systems.

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