Butyryl Chitosan : Synthesis, Characterization and Evaluation of the Sustained Release Performance as Tacrolimus Carrier

Chitosan and its water-soluble derivatives have been widely used in biomaterials, but their disadvantages have hindered their widespread application. In this study, butyryl chitosan, a liposoluble chitosan derivative, was prepared by introducing butyryl groups into chitosan molecules through an acylation reaction. The synthesis conditions were optimised, the reaction was more efficient and simpler than previously reported strategies. Two butyryl chitosan with degrees of substitution greater than two were synthesised. Chemical characterisations confirmed that the hydroxyl and primary amine groups in the backbone of chitosan were converted into amide and ester groups, respectively. The butyryl chitosan films have advantages such as high mechanical properties, long biodegradation time, proper surface charge, good cytocompatibility, and histocompatibility. Butyryl chitosan was used as carrier to prepare an implantable tacrolimus sustained release film. The blood concentration of sustained release tacrolimus implanted subcutaneously in rats could be maintained the time window of treatment within 11 days. The implantable tacrolimus sustained release film could provide a systemic exposure similar to that of oral and injectable preparations but lower intrapatient variability in tacrolimus trough levels. We expect an improvement in terms of therapeutic compliance with positive effects on allograft outcomes