Chitosan Hydrogels with Embedded Thermo- and pH-Responsive Microgels as a Potential Carrier for Controlled Release of Drugs.

We report a promising strategy based on chitosan (CS) hydrogels and dual temperature- and pH-responsive poly(-isopropylacrylamide--methacrylic acid) (PNIPAM--MAA) microgels to facilitate release of a model drug, moxifloxacin (MFX). In this protocol, first, the microgels were prepared using a free radical copolymerization method, and subsequently, these carboxyl-group-rich soft particles were incorporated inside the hydrogel matrix using an EDC-NHS amidation method. Interestingly, the resulting microgel-embedded hydrogel composites (MG-HG) acting as a double barrier system largely reduced the drug release rate and prolonged the delivery time for up to 68 h, which was significantly longer than that obtained using microgels or hydrogels alone (20 h). On account of the dual-responsive features of the embedded microgels and the variation of water-solubility of drug molecules as a function of pH, MFX could be released in a controllable manner by regulating the temperature and pH of the delivery medium. The release kinetics followed a Korsmeyer-Peppas model, and the drug delivery mechanism was described by Fickian diffusion. Both the gel precursors and the hydrogel composites exhibited low cytotoxicity against mammalian cell lines (HeLa and HEK-293) and no deleterious hemolytic activity up to a certain higher concentration, indicating excellent biocompatibility of the materials. Thus, the unprecedented combination of modularity of physical properties caused by soft particle entrapment, unique macromolecular architecture, biocompatibility, and the general utility of the stimuli-responsive polymers offers a great promise to use these composite materials in drug delivery applications.