浅谈主动载药法制备硫酸卷曲霉素脂质体及其质量评价.docVIP

浅谈主动载药法制备硫酸卷曲霉素脂质体及其质量评价 论文联盟www.LWLM.com编辑。 【摘要】 目的 制备硫酸卷曲霉素脂质体，建立含量和包封率的测定方法，初步考察其体外释放规律。方法 采用pH梯度法制备硫酸卷曲霉素脂质体，超滤法分离脂质体与游离药物，RPHPLC测定脂质体的含量和包封率，透析法考察脂质体的体外释放行为。结果 超滤法能很好地将脂质体与游离药物分离，测定硫酸卷曲霉素脂质体的含量为10.27mg/ml，包封率为47.8%，脂质体的体外释放规律符合一级动力学过程。结论 pH梯度法适于制备硫酸卷曲霉素脂质体，超滤法可用于硫酸卷曲霉素脂质体包封率的测定，制备的脂质体具有一定的缓释效果。 【关键词】 硫酸卷曲霉素； 脂质体； pH梯度法； 包封率； 体外释放 ABSTRACT Objective To prepare capreomycin sulfate liposomes to develop a method for determining its drug content and entrapment efficiency and to study the release profile in vitro. Methods Capreomycin sulfate was encapsulated into the liposomes using the pH gradient dependent remote loading technique. Free capreomycin sulfate and liposomes were separated by ultrafiltration, RPHPLC was applied to determine the entrapment efficiency and dialysis was utilized to study the release behavior of drug from liposome in vitro.Results Free capreomycin sulfate and liposomes was well separated by ultrafiltration. The content and entrapment efficiency of capreomycin sulfate liposomes determined were 10.27mg/ml and 47.8% respectively. The release profile in vitro was subjected to the first order model. Conclusion The pH gradient technique is suitable for preparing capreomycin sulfate liposomes which exhibits sustainedrelease profile in vitro. Ultrafiltration established in this study can be applied in the determination of entrapment efficiency of capreomycin sulfate liposomes. KEY WORDS Capreomycin sulfate;Liposome;pH gradients;Entrapment efficiency;in vitro release 硫酸卷曲霉素(capreomycin sulfate，CS)是一种对结核分枝杆菌有效的抗生素，结构式如Fig.1。由于其对链霉素、卡那霉素耐药的肺结核患者仍有效，因而在抗结核治疗中具有重要价值，常作为二线抗结核药［1］。目前，CS的临床使用剂型多为肌肉注射和静脉滴注。肌肉注射由于局部硬结、疼痛等不良反应，患者无法耐受，致使用药中断，治疗失败。CS的不良反应主要为耳毒性和肾毒性， 因此有必要利用合理的给药系统，降低其毒副作用，提高临床疗效。 脂质体作为一种安全有效的药物载体，通过与细胞膜发生融合和作用提高治疗效果。已有多种抗生素药物制成脂质体药物传递系统，取得了较好的疗效［2］。脂质体对水溶性药物包封率不高，采用薄膜分散法制备CS脂质体，包封率仅达13%［3］。本实验进行了主动载药法制备CS脂质体，以期获得较高的包封率。 1 仪器与试药Fig.1 The structure formula of capreomycin 岛津高效液相色谱仪(LC10AT泵，SPD10A紫外检测器，N2010工作站)，超声波细胞粉碎机(宁波新芝科