Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitos...Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5'-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate (TPP) to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy (TEM), and their zeta potential, particle size, and polydispersity (size distribution) were measured by the dynamic light scattering (DLS) techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.展开更多
基金Funded by the National Natural Science Foundation of China(Nos.20504018,20972014,20604010,20872010 and 20732004)the National Basic Research Program of China(No.2009CB930203)
文摘Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5'-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate (TPP) to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy (TEM), and their zeta potential, particle size, and polydispersity (size distribution) were measured by the dynamic light scattering (DLS) techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.
