Injectable chitosan-based hydrogel for implantable drug delivery: body response and induced variations of structure and composition.

Abstract

Thermosensitive hydrogel composed of chitosan and glycerophosphate (CS/GP) is proposed to be the potential candidate of in situ gel-forming implant for long-term drug delivery. The present study was focused on the body response and induced structural and componential variations of the hydrogel, which were considered to impact on the drug delivery significantly but were scarcely reported. The body response was investigated by histological examination. It showed that the hydrogel caused an inflammatory response immediately after being implanted into Sprague-Dawley (SD) rats. The inflammatory response was mainly exhibited as inflammatory cell surrounding and infiltrating, tissue encapsulating, and vascularization in tissue. The effects of the inflammatory response on the structure and component of the CS/GP hydrogel were extensively explored through analyzing the hydrogel samples taken by surgery. The tissue encapsulation and osmotic pressure caused the water loss of the hydrogel and the compaction of the hydrogel network, and resulted in the porosity decreasing. The cell surrounding and infiltrating spawned big pores in the network and generated the subdivision of the network. All these structural and componential variations of the hydrogel in vivo were quite different from those in vitro and were supposed to exert significantly effects on drug release kinetics.