Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.
