The Research On10-Hydroxycamptothecin Loaded Pegphdcananoparticles

10-hydroxycamptothecin (HCPT) is an insoluble derivatives extracted from camptotheca acuminata decaisne. HCPT is a promising anticancer agent against a broad spectrum of cancers such as stomach cancer, live cancer, leucocythemia and rectal cancer etc. However, the clinical utilization is greatly limited by its instability and poor solubility in both water and organic solvents. In order to reduce side effect and improve stability, HCPT loaded PEGPHDCA nanoparticles is prepared in present study, including:MePEG cyanoacetate and hexadecyl cyanoacetate was synthesized by the esterification of cyanoacetic acid with MePEG and hexadecanol. A new amphipathic copolymer poly (PEG cyanoacrylate-co-hexadecyl cyanoacrylate)(PEGPHDCA) was synthesized in the presence of formalin and pyrrolidine. Structure of the products was confirmed by FTIR and1H-NMR spectroscopy. The molecular weight and melting point was determined by Gel Permeation Chromatography (GPC) and differential scanning calorimetry (DSC) respectively.A precise and convenient HPLC method was established to determine the concentration of HCPT. The apparent solubility in water and octanol was determined. The apparent partition coefficient in octanol/water was9.49. The pKa was calculated from the process of carboxylate form of HCPT into lactones form in different pH solution.HCPT loaded PEGPHDCA nanoparticles prepared by film dispersion and hydration-sonication method. The influence of HCPT, cholesterol, PEGPHDCA and ultrasonic power was investigated by one-factor experiment. The optimized prescription was obtained by central composite design and response surface methodology.The nanoparticles prepared with optimized prescription demonstrated good stability, the encapsulation efficiency was more than80%, the average size was141.6±6.7nm, the Zeta potential was-18.2±2.2mV and drug loading content was2.92±0.21%。In vitro drug release and in vivo pharmacokinetics of HCPT nanoparticles were compared with those of HCPT injection. The results demonstrated that the nanoparticles remarkably prolonged in vitro the release time and in vivo half life respectively. All studies in this paper demonstrated that PEGPHDCA nanoparticles seem to be a appropriate delivery system for HCPT.