Development and characterization of temperature responsive hydrogel nanoparticle system

Abstract

Poly(N-isopropylacrylamide-co-acrylic acid) hydrogel nanoparticles were prepared by free radical copolymerization of N-isopropylacrylamide and acrylic acid in the presence of crosslinker above lower critical solution temperature (LCST). They exhibited a reversible swelling and deswelling behavior: ca. 200 nm diameter below the LCST and ca. 100 nm diameter above the LCST. The nanoparticles were tagged with fluorescent dye (FITC) in order to monitor the extent of cellular uptake and were further modified with galactose moieties to evaluate the extent of receptor-mediated endocytosis against HepG2 cells. Flow cytometry and confocal microscopy were used to investigate cellular uptake behaviors of the nanoparticles. It was found that the extent of cellular uptake of nanoparticles was far greater above the LCST than below the LCST, suggesting that smaller nanoparticles were taken up more readily within cells. When the nanoparticles were galactosylated, the extent of cellular uptake increased dramatically due to receptor-mediated endocytosis. Novel Pluronic/heparin composite nanocapsules that exhibit a thermally responsible swelling and deswelling behavior were synthesized. Pluronic F-127 pre-activated with pnitrophenyl chloroformate at its two terminal hydroxyl groups was dissolved in a methylene chloride phase. The organic phase was dispersed in an aqueous phase containing heparin. At an organic/aqueous interface, Pluronic-crosslinked heparin nanocapsules were produced. They exhibited a 1,000-fold volume transition (ca. 336 nm at 25℃; ca. 32 nm at 37℃), and a reversible swelling and deswelling behavior when the temperature was cycled between 20℃ and 37℃. The reversible volume transition of Pluronic nanocapsules was caused by micellization and demicellization of cross-linked Pluronic polymer chains within the nanocapsule structure in response to temperature. The morphological characters were investigated with transmission electron microscopy and small angle neutron s...