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. Characterization results showed that tacrolimus existed in an amorphous state in the release film. This work embodies an innovative formulation using tacrolimus-loaded carboxymethyl chitosan amorphous solid dispersions embedded butyryl chitosan film with added advantage of sustained release, an effective blood concentration in vivo for 11 days and a systemic exposure but lower intrapatient variability in tacrolimus trough levels. This work merits sustainable tacrolimus release use by providing application-based proofs and qualifies as a potential formulation for sustainable tacrolimus release system. We expect an improvement in terms of therapeutic compliance with positive effects on allograft outcomes.

Automated summary

In this study, a liposoluble chitosan derivative, butyryl chitosan, was successfully prepared by introducing butyryl groups into chitosan molecules through an acylation reaction. The butyryl chitosan films exhibited high mechanical properties, long biodegradation time, proper surface charge, good cytocompatibility, and histocompatibility. The butyryl chitosan was also used as a carrier for a sustained release film, and the characterization results showed an amorphous state of the drug in the film. This work demonstrates the potential of butyryl chitosan as a sustainable drug delivery system.