Lichtenstein A, Margalit R
Department of Biochemistry, Tel Aviv University, Israel.
J Inorg Biochem. 1995 Nov 15;60(3):187-98. doi: 10.1016/0162-0134(95)00019-k.
Liposomes encapsulating silver sulfadiazine (SSD), the drug of choice for topical treatment of infected burns, are investigated as an improved delivery system that could act as a locally targeted sustained-release drug depot. This communication reports the first stage of the investigation and is focused on (a) the development of spectrophotometric assays for liposome-encapsulated and for free (aqueous soluble) and SSD, (b) on evaluation of the efficiency of encapsulation and kinetics of drug release. DMSO containing 140 mM NH3 was found to be the best solvent for dissolution of the liposomes and for determination of their SSD content. Peak absorption of liposome-originating SSD in this solvent is at 263 nm with em values of 23 x 10(3)-26 x 10(3). Peak absorption of SSD in aqueous solutions is at 254 nm with em magnitudes varying from 2 x 10(3) to 23 x 10(3), depending on the electrolytic composition of the system. Kinetic studies of drug release and separations by centrifugation and by gel-exclusion chromatography all indicate that the SSD in the liposomal system is distributed among three states: encapsulated, soluble unencapsulated, and stable (unencapsulated) aggregates that reside in the aqueous phase in which the liposomes are suspended. The liposomal SSD systems were found to meet the essential requirements of high-efficiency encapsulation and sustained drug release. Encapsulation efficiencies of > 80% at 10 mM lipid, reaching up to 95% at 100 mM lipid, were obtained. The release of encapsulated SSD follows first-order kinetics, with half-life up to 24 hr and with sensitivity to the electrolytes in the system. It is concluded that SSD-liposomal systems are feasible, have potential benefits over treatment with free SSD, and merit further pursuit into providing local targeting.
脂质体包裹的磺胺嘧啶银（SSD）是治疗感染烧伤的首选局部用药，作为一种改进的给药系统进行了研究，它可作为局部靶向的缓释药物储存库。本通讯报道了研究的第一阶段，重点在于：（a）开发用于测定脂质体包裹的、游离（水溶性）的SSD的分光光度法；（b）评估包封效率和药物释放动力学。发现含140 mM NH₃的DMSO是溶解脂质体及其SSD含量测定的最佳溶剂。在此溶剂中，脂质体来源的SSD的峰值吸收在263 nm处，吸光系数值为23×10³ - 26×10³。SSD在水溶液中的峰值吸收在254 nm处，吸光系数大小根据系统的电解质组成在2×10³至23×10³之间变化。药物释放的动力学研究以及通过离心和凝胶排阻色谱法进行的分离均表明，脂质体系统中的SSD分布在三种状态：包裹的、未包裹的可溶性和稳定（未包裹）聚集体，这些聚集体存在于脂质体悬浮的水相中。发现脂质体SSD系统满足高效包封和持续药物释放的基本要求。在10 mM脂质时包封效率> 80%，在100 mM脂质时高达95%。包裹的SSD的释放遵循一级动力学，半衰期长达24小时，并且对系统中的电解质敏感。结论是，SSD脂质体系统是可行的，与游离SSD治疗相比具有潜在优势，值得进一步研究以实现局部靶向。
