Self-assembled nanoparticles from thermo-sensitive polyion complex micelles for controlled drug release

Self-assembled nanoparticles from thermo-sensitive polyion complex (PIC) micelles comprised of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-isopropylacrylamide) [P(tBA-co-AA)-b-PNIPAM] core–shell micelles and graft copolymer chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAM) were developed for applications in controlled drug release. The PIC micelles nanoparticles had a multi-layer core–shell–corona structure with hydrophobic PtBA as the inner core, negatively charged PAA and positively charged CS forming the middle layer as the shell, and thermo-sensitive PNIPAM as the outer corona. The molar ratio of P(tBA-co-AA)-b-PNIPAM to CS-g-PNIPAM affected the functionalities and hydrodynamic diameters of nanoparticles. Release of doxorubicin (DOX) from micelles was suppressed at neutral solutions due to the stability of electrostatic interactions but accelerated at acidic solutions or high temperatures above LCST. This study presents new micelles with a functional inner shell whose structure can be rapidly damaged to release charged drugs when the microenvironment of micelles changed.

► Nanoparticles from thermo-sensitive PIC micelles were formed by P(tBA-co-AA)-b-PNIPAM and CS-g-PNIPAM.
► Complexation and release of DOX from PIC micelles nanoparticles was studied.
► This study presents a new micelles structure for controlled drug release.