Smart composite materials based on chitosan microspheres embedded in thermosensitive hydrogel for controlled delivery of drugs

Smart composite hydrogels (SCHs) consisting of chitosan (CS) microspheres physically embedded within a thermoresponsive hydrogel are synthesized and tested for their capacity of loading and long-term release of a small molecule drug. CS microspheres were used since they display pH-sensitive properties and have the capacity to bind electrostatically the opposite charged salicylic acid (SA), taken as model drug. These microspheres are ulterior physically entrapped within a thermoresponsive hydrogel based on poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) copolymer, cross-linked with N,N'-methylenebisacrylamide. The morphology, swelling behavior, temperature and pH sensitivity, degradability and drug release behavior of the new smart drug delivery system were investigated. Swelling ratios as well as the sharpness of the phase transition, largely depended on the cross-linking degree. The thermoresponsive network slightly protected the CS microspheres from the in vitro degradation. In vitro studies showed that the SA followed a prolonged release profile from SCHs in accordance with pH and temperature.