| 摘要 |
Novel compositions of nucleotide analog prodrugs for the treatment of viral infections and cancer are herein disclosed. The prodrugs have a biocompatible polymeric carrier conjugated to the nucleotide analog via an amino-phosphate linkage. The amino group is provided by the carrier, which either inherently possesses a primary amine, or is modified with reactive groups that incorporate the primary amine onto the carrier. The carrier can be a polyamino acid, a polyvinylic polymer, a polysaccharide or combinations thereof, such as polylysine, HPMA, dextran, hydroxyethyl starch, or polyethylene glycol; the nucleotide analog can be ribavirin araA, AZT, acyclovir, 5-FUDR, araC or ddI. Methods of treating a viral infection of cancer using these prodrugs are also disclosed. The prodrugs endow the nucleotide analogs with substantially enhanced therapeutic efficacy and reduces toxicity in comparison to the nucleotide analog alone. |
