Synthesis and characterization of camptothecin-polyethylene glycol ester prodrugs

To improve the metabolic stability of camptothecin (CPT) in vivo,a series of 20-PEG-linked camptothecin prodrugs were synthesized.After activation of hydroxy groups at the two ends of polyethylene glycol (PEG),CPT was coupled to the activated PEG to give the targeted products 6a-6e .The chemical structures of 6a-6e were characterized by IR and ¹H NMR.HPLC method was used for the determination of CPT concentration in PBS buffer (pH 7.4) and in plasma of rats.Drug releasing rates from 6a-6e in PBS buffer (pH 7.4) were 11%-52% within 24 h.When given to rats intravenously,AUC of compounds 6a-6e were 4.38 to 6.67 fold higher than that of CPT solution.Compunds 6a-6e have longer circulation effects,substantially greater than CPT.They can prolong biological half-life and improve the bioavailability of camptothecin.