Polymeric nanostructures with pH-labile core for controlled drug release

Abstract

Efficient and stimuli-triggered controlled delivery of therapeutics is one of the important issues in modern advanced therapy. In the present work, a versatile route for the synthesis of core cross-linked polymeric nanostructures (CLPN) through thiol-acrylate Michael addition reaction via the formation of β-thiopropionate has been described. The acid groups of the poly(acrylic acid) block of poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(acrylic acid) triblock copolymer were reacted with 2-hydroxyethyl acrylate (HEA) to yield the corresponding acrylate-functionalized copolymer (P1). Following this, P1 was reacted with a thiol functionalized cross-linker (CL) resulting in the formation of core cross-linked polymeric nanoparticles through acrylate-thiol Michael reaction. The ability of these nanoparticles to encapsulate drug molecules inside their core and their effective release following a pH-triggered controlled degradation of the core were demonstrated. The temperature sensitive release behaviour of the system was also studied. The non-toxic nature of the precursor polymers and the core cross-linked polymeric nanoparticles was also established, that further substantiated their potential as carriers for controlled release of drugs.

Keywords: Block copolymers; Polymer colloids; Prednisolone; RAFT polymers; Thermosensitive release; Thiol–acrylate Michael addition; pH-triggered degradation.