Vakilzadeh Hamed, Varshosaz Jaleh, Minaiyan Mohsen
Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmacology, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Curr Drug Deliv. 2018;15(5):630-640. doi: 10.2174/1567201815666180209113735.
Triptorelin, the synthetic analog of gonadotrophin-releasing hormone, is used for the treatment of sex hormone dependent diseases via parenteral administration. The aim of the present study was to investigate the possibility of triptorelin pulmonary delivery and preparation of a pulmonary nanocarrier delivery system for it.
Triptorelin was loaded in Pluronic-F127 grafted poly (methyl vinyl ether-alt-maleic acid) nanomicelles by direct dissolution method. Effects of the processing variables including: drug/polymer ratio, temperature, stirring rate and time on the physicochemical properties of nanomicelles including zeta potential, particle size, drug entrapment efficiency and release profiles of triptorelin loaded nanomicelles were evaluated. For animal studies 24 Wistar rats were separated into four groups of six. Group 1 received blank nanomicelles, groups 2, 3 and 4 were treated with a single dose of 250 µg.kg-1 of triptorelin solution subcutaneously (sc), pulmonary spraying of triptorelin solution (250 µg.kg-1) and pulmonary spraying of triptorelin nanomicelles (250 µg.kg-1), respectively by microsprayer.
The optimized micelles had particle size of 87.35 nm, zeta potential of -12.8 mV, entrapment efficiency of 84.36% and release efficiency of 65%. The area under the blood testosterone levels increment differed significantly (p<0.05) between pulmonary triptorelin nanomicelles and drug solution. The pharmacological activity of the simple solution was 59.38%, while it was 80.18% for the nanomicelles relative to sc route of administration with prolonged residence time.
The results of this study show that not only triptorelin is absorbable from the lungs but also nanomicelles can significantly enhance its pulmonary absorption compared to its simple solution.
曲普瑞林是促性腺激素释放激素的合成类似物，通过肠胃外给药用于治疗性激素依赖性疾病。本研究的目的是探讨曲普瑞林肺部给药的可能性，并为其制备肺部纳米载体给药系统。
采用直接溶解法将曲普瑞林载入普朗尼克-F127接枝聚（甲基乙烯基醚-alt-马来酸）纳米胶束中。评估了包括药物/聚合物比例、温度、搅拌速率和时间在内的工艺变量对纳米胶束物理化学性质的影响，这些性质包括ζ电位、粒径、药物包封率以及载药纳米胶束的释放曲线。在动物研究中，将24只Wistar大鼠分为四组，每组6只。第1组接受空白纳米胶束，第2、3和4组分别通过微量喷雾器皮下注射（sc）单剂量250 μg·kg-1的曲普瑞林溶液、肺部喷雾曲普瑞林溶液（250 μg·kg-1）和肺部喷雾曲普瑞林纳米胶束（250 μg·kg-1）。
优化后的胶束粒径为87.35 nm，ζ电位为-12.8 mV，包封率为84.36%，释放率为65%。肺部曲普瑞林纳米胶束和药物溶液之间血睾酮水平升高的曲线下面积差异显著（p<0.05）。相对于皮下给药途径且具有延长的停留时间，单纯溶液的药理活性为59.38%，而纳米胶束的药理活性为80.18%。
本研究结果表明，曲普瑞林不仅可从肺部吸收，而且与单纯溶液相比，纳米胶束可显著增强其肺部吸收。
