【摘要】 目的:采用pH梯度法制备脂质体米托蒽醌并研究其稳定性、毒性和抑瘤药效.方法:以国产卵磷脂和胆固醇为膜材,薄膜-挤压法制备粒径均一的大单室脂质体,利用跨膜pH梯度载药法制备米托蒽醌脂质体,测定其载药率,考察该制剂及磷脂辅料的稳定性.以荷瘤小鼠为模型研究脂质体米托蒽醌的毒性和抑瘤效果.结果:该方法可以获得平均粒径110nm的大单室脂质体,pH梯度载药的包封率可以高达97%.在低温条件未发生药物泄露.药物和卵磷脂的水解也不明显.脂质体米托蒽醌显著降低了药物毒性,提高了药物的抗癌效果.结论:国产磷脂辅料,薄膜-挤压法制备大单室脂质体,pH梯度载药制备脂质体米托蒽醌是可行的工艺方法.动物实验表明脂质体米托蒽醌可以降低毒性,有很好的抗肿瘤作用.更多还原

【Abstract】 AIM:To prepare liposomal mitoxantrone by pH-gradient drug loading technique and study the stability of formulation,toxicity and anti-tumor efficacy.METHODS:The large unilamellar vesicles were prepared by the film-extrusion method with domestic egg phosphacholine(EPC)and cholesterol.Liposomal mitoxantrone was prepared by pH-gradient drug loading technique.The drug loading efficiency,the stability of drug and EPC were investigated.The toxicity and anti-tumor activity were evaluated in tumor-bearing mouse.RESULTS:The large unilamellar vesicles with an average particle size of 110 nm were obtained.The drug encapsulation efficiency reached 97%.Under low temperature there was no observed drug release,neither detectable drug degradation nor lipid hydrolization.The mitoxantrone encapsulated into liposomes reduced dramatically the drug related toxicity,and enhanced anti-tumor activity.CONCLUSION:It is a practically acceptable formulation process by film-extrusion method and domestic phosphalipids.It has been demonstrated that liposomal mitoxantrone can reduce drug toxicity and show good anti-tumor activity.更多还原