Desai Sandhya K, Naik Suresh R
Department of Pharmacology, Prin. K. M. Kundnani College of Pharmacy, Mumbai, India.
J Liposome Res. 2008;18(4):279-92. doi: 10.1080/08982100802457336.
The research work was designed to compare the relative toxicity, chemotherapeutic activity, and pharmacokinetic parameters of liposomal incorporated SJA-95 with that of free SJA-95, with an objective to reduce toxicity and improve therapeutic activity in vivo. Liposomal-incorporated SJA-95 (Lip SJA-95), prepared using the proliposome method, was found to exhibit a higher LD(50) value in mice, and the relative toxicity was about 2.5 times lower than that of the free drug. Lip SJA-95 treatment in experimental mice model of Candidiasis showed increased survival and reduced fungal loads in various organs. The pharmacokinetic profile of the free and liposomal drug was evaluated by administration of free and Lip SJA-95 intravenously to healthy albino rabbits in a crossover fashion. Lip SJA-95 showed an initial fall in plasma levels and longer half-life. The improved microbial clearance following treatment with Lip SJA-95 could be attributed partly to an increased tissue uptake, which was reflected in a marked increase in volume of distribution (V(d)) and longer half-life (T(1/2)). The present results clearly indicated that Lip SJA-95 treatment led to prolonged survival time, effective microbiological clearance, and reduced toxicity in the mice model of Candidiasis.
本研究工作旨在比较脂质体包裹的SJA - 95与游离SJA - 95的相对毒性、化疗活性和药代动力学参数，目的是降低毒性并提高体内治疗活性。采用前体脂质体法制备的脂质体包裹的SJA - 95（Lip SJA - 95）在小鼠中表现出较高的半数致死量（LD(50)）值，其相对毒性比游离药物低约2.5倍。在念珠菌病实验小鼠模型中，Lip SJA - 95治疗显示存活率提高，各器官中的真菌载量降低。通过以交叉方式给健康白化兔静脉注射游离SJA - 95和Lip SJA - 95来评估游离药物和脂质体药物的药代动力学特征。Lip SJA - 95显示血浆水平初始下降且半衰期更长。用Lip SJA - 95治疗后微生物清除率提高，部分原因可能是组织摄取增加，这反映在分布容积（V(d)）显著增加和半衰期（T(1/2)）延长。目前的结果清楚地表明，在念珠菌病小鼠模型中，Lip SJA - 95治疗可延长存活时间、有效清除微生物并降低毒性。
