抗癌药物羟基喜树碱纳米囊泡的研究

Study on the preparation and characterization of 10-Hydroxycamptothecin loaded PEG-PHDCA nanoparticles

羟基喜树碱(Hydroxyeamptothecin,HCPT)是对多种癌症都有较好疗效的广谱抗癌药物,然而极低的脂水溶解性和不稳定性极大地限制了该药物的临床运用.合成了聚乙二醇化聚十六烷基氰基丙烯酸酯[poly(PEG cyanoacrylate-co-hexadecyl cyanoacrylate),PEG-PHDCA],并以此为载体材料,采用薄膜水化超声法制备HCPT的PEG-PHDCA纳米囊泡,并对其进行初步的理化性质和体内外释药特性的考察.制备得到的HCPT的PEG-PHDCA纳米囊泡平均粒径为(141.6±6.7)nm,平均ξ电位为(-18.2±2.2)mV,平均载药率为(2.92±0.21)%,平均包封率为(83.8±2.5)%.体内外释药实验表明:本实验制备的纳米囊泡制剂能有效延长释药时间,提高HCPT的稳定性、水溶性,是一种很有研究价值的剂型.

10-Hydroxycamptothecin （HCPT） has shown broad anticancer activity, but its instability and poor solubility in both water and organic solvents has limited its use in clinical practice. Poly （PEG cyanoacrylate-co-hexadecyl cyanoacrylate） PEG-PHDCA was synthesized and HCPT-loaded PEG-PHDCA nanoparticles were prepared by film-dispersion and hydrationsonication technique. The result showed that the average size of the prepared nanoparticles was （141.6±_6.7） nm, the Zeta potential was （-18.2±2.2） mV and drug loading content was （2.92 ±0.21） %, the average encapsulation efficiency was （83.8±2.5）%. In vitro drug release and in vivo pharmacokinetics of HCPT nanoparticles were compared with those of HCPT. The results demonstrated that the nanoparticles remarkably prolonged in vitro release time and in vivo half life respectively. All studies in this paper revealed that PEG-PHDCA nanoparticles seem to be an appropriate delivery system for HCPT.