Well-defined amphiphilic poly(ε-caprolactone)-b-poly(N-isopropylacrylamide) and thermosensitive micelles formulation

Polymeric nanoparticles, based on amphiphilic copolymers, have been extensively evaluated as a potential material for drug delivery systems (DDS), because they present a clear capability of forming micelles under an aqueous medium. Besides the amphiphilic properties, the thermosensitivity of polymers under aqueous media has attracted great attention for DDS. In this work, a well-defined amphiphilic poly(ε-caprolactone)-b-poly(N-isopropylacrylamide) (PCL-b-PNIPAAm) was used to prepare thermosensitive micelles as potential candidates for applications in drug delivery systems. First, hydroxyl-terminated PCL (PCL-OH) was synthesized by ROP, and then, the PCL-OH was converted to PCL-Br through reaction with 2-bromopropionyl bromide, followed by a chemical modification to ethyl xanthate in PCL-end chains through substitution reaction. The PCL-b-PNIPAAm block copolymers were obtained by RAFT polymerization of N-isopropylacrylamide (NIPAAm) monomer from the PCL-EX macroagent. Different size chains of PCL and PNIPAAm were evaluated as also their influence on the capacity of micelles formation. The polymers and their synthesis efficacy were characterized by chemical composition, molecular weight, and thermal and crystallinity properties. The CMC of the copolymers and the LCST of the micelles increased with the increase in the segmental length of PNIPAAm and decreased with the increase in PCL segmental length. The DLS demonstrated an increase in the micelles size with the increase of the proportion of both hydrophobic and hydrophilic segments. Finally, the morphology observed by AFM demonstrated that the micelles are of spherical shape.

Graphical abstract