Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications.

Thermogelling chitosan (CS)/glycerophosphate (GP) solutions have been reported as a new type of parenteral in situ forming depot system. These free-flowing solutions at ambient temperature turn into semi-solid hydrogels after parenteral administration. Formulation parameters such as CS physico-chemical characteristics, CS/gelling agent ratio or pH of the system, were acknowledged as key parameters affecting the solution stability, the sol/gel transition behavior and/or the final hydrogel structure. We discuss also the use of the standard CS/GP thermogels for various biomedical applications, including drug delivery and tissue engineering. Furthermore, this manuscript reviews the different strategies implemented to improve the hydrogel characteristics such as combination with carrier particles, replacement of GP, addition of a second polymer and chemical modification of CS. The recent advances in the formulation of CS-based thermogelling systems already overcame several challenges faced by the standard CS/GP system. Dispersion of drug-loaded carrier particles into the thermogels allowed achieving prolonged release profiles for low molecular weight drugs; incorporation of an additional polymer enabled to strengthen the network, while the use of chemically modified CS led to enhanced pH sensitivity or biodegradability of the matrix.