Novel synthesis and in vitro drug release of polymeric prodrug: Chitosan–O-isopropyl-5′-O-d4T monophosphate conjugate

A novel approach to synthesize chitosan–O-isopropyl-5′-O-d4T monophosphate conjugate was developed. Chitosan-d4T monophosphate prodrug with a phosphoramidate linkage was efficiently synthesized through Atherton-Todd reaction. In vitro drug release studies in pH 1.1 and 7.4 indicated that chitosan–O-isopropyl-5′-O-d4T monophosphate conjugate prefers to release the d4T 5′-(O-isopropyl)monophosphate than free d4T for a prolonged period. The results suggested that chitosan–O-isopropyl-5′-O-d4T monophosphate conjugate may be used as a sustained polymeric prodrug for improving therapy efficacy and reducing side effects in antiretroviral treatment.

Graphical abstractThis work describes the novel synthesis of chitosan–O-isopropyl-5′-O-d4T monophosphate conjugate, allowing a sustained release of d4T 5′-(O-isopropyl)monophosphate for antiretroviral treatment.Figure optionsDownload full-size imageDownload as PowerPoint slide