Synthesis and physico-chemical characterization of a β-cyclodextrin conjugate for sustained release of Acyclovir

We report the synthesis of an oligomeric prodrug of the antiviral agent Acyclovir (Acy) conjugated to beta-cyclodextrin (beta-CyD). The drug was selectively linked through a succinic spacer to one of the primary hydroxyl groups of beta-CyD by ester linkage in a 1:1 molar ratio. The conjugate was purified by semipreparative reverse-phase chromatography and characterized by FAB mass spectrometry and NMR experiments. The release of Acy from the conjugate was evaluated both in acidic and in neutral conditions and in the presence of porcine liver esterase. In all cases we observed the release of both free Acy and Acy succinate (AcySucc) at differing rates as a function of the hydrolysis conditions. In the presence of esterase the release of free Acy was favoured over AcySucc, showing a release rate of 100% of Acy within 7 days.