A facile method for synthesizing water-soluble and superior sustained release anti-HIV prodrug SCs-d4T

To efficiently deliver stavudine (d4T) for AIDS therapy, chitosan-stavudine conjugate (Cs-d4T) was synthesized. However, its poor water-solubility limited its clinical application. In this study, a sulphonated chitosan-stavudine conjugate (SCs-d4T) was synthesized with a mild SO3·Py complex sulphonation strategy. Chemical characteristics and morphology of Cs-d4T and SCs-d4T were performed by NMR, XRD, FTIR, ICP-AES and SEM. SCs-d4T demonstrated satisfactory solubility (106-bold of Cs-d4T solubility), good anti-HIV activity (6-fold of d4T anti-HIV activity), and well sustained release ability. The major release product O-isopropyl-5'-H-phosphonate of d4T (d4T-P-H) showed higher anti-HIV activity than d4T. For further evaluating the influence of linker and sulphonation strategy on anti-HIV activity, chitosan grafted with d4T by succinyl linker (Cs-sd4T) and SCs-d4T sulphonated by oleum were also prepared. The result showed that the O-isopropyl monophosphate linker of Cs-d4T and SO3·Py complex sulphonation strategy revealed higher anti-HIV activity than succinyl linker of Cs-sd4T and oleum sulphonation strategy, respectively.