Synthesis, Characterization and Aggregation Behavior of Polyethylene Glycol-conjugated Hydroxycamptothecin

Methoxypolyethylene glycol(MPEG)-conjugated hydroxycamptothecin(HCPT), denoted as MPEG-HCPT, was synthesized via etherification reaction between terminal hydroxyl of MPEG and 10-hydroxy of HCPT, and they were characterized via H-1 NMR and FTIR. The effect of MPEG conjugation on the solubility and lactone-ring stability of HCPT was investigated, as well as its aggregation behavior. The mass fraction of HCPT in the derivative was approximately 33% and the solubility of the MPEG-HCPT in buffer solutions of pH 4. 8 and 7. 2 at 37 degrees C were respectively 5. 23 and 7. 90 mmol/L, significantly higher than those of pristine HCPT (0. 0026 and 0. 035 mmol/L). The pK(ah)(K-ah, the apparent hydrolysis equilibrium constant) of MPEG-HCPT at 37 degrees C was determined to be approximately 7. 12, higher than that of pristine HCPT (ca. 6. 67), indicating that the MPEG conjugation could enhance the lactone-ring stability of HCPT. The MPEG-HCPT exhibited obvious surface activity, and could form aggregates in water with a aggregation micelle concentration of 0. 46 mmol/L.