Synthesis of Chitosan-Based Thermo- and pH-Responsive Porous Nanoparticles by Temperature-Dependent Self-Assembly Method and Their Application in Drug Release

In this research, thermo- and pH-responsive chitosan-based porous nanoparticles were prepared by the temperature-dependent self assembly method. The chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNTPAAm) copolymer solution was prepared through polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using cerium ammounium nitrate as the initiator. Then, CS-g-PNIPAAm solution was diluted by deionized water and heated to 40 degrees C for CS-g-PNIPAAm self-assembly. After that, CS-g-PNIPAArn assembled to form micelles in which shell layer was CS. Crosslinking agent was used to reinforce the micelle structure to form nanoparticle. The molar ratio of CS/NIPAAm in the feed mixture was changed to investigate its effect on structure, morphology, thermal- and pH-responsive properties of the nanoparticles. TEM images showed that a porous structure of nanoparticles was developed. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli-responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in-vitro release experiment. These porous particles with environmentally sensitive properties are expected to be utilized in hydrophilic drug delivery system. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5126-5136, 2009