摘要
为解决抗艾滋药物两亲性脂肽LP-98溶解度低的问题,采用高压均质技术制备LP-98纳米混悬液冻干粉,并对其进行理化性质表征及药代动力学研究。最优制备工艺为:稳定剂为SDS,浓度为0.80wt%,高压均质压力为150 MPa,高压均质次数为5次。制备得到的LP-98纳米混悬液冻干粉复溶后平均粒径为261.5±1.1 nm,Zeta电位为-31.5±0.2 m V。圆二色光谱仪与单周期病毒感染实验结果显示LP-98的结构与生物活性均未改变。药代动力学结果表明,LP-98纳米混悬液冻干粉生物利用度为原料药的98.1%。LP-98在水中溶解度由184μg/m L提升至1733μg/m L,与原料药相比提高了8倍,解决了注射时药物难混悬的问题。
AIDS has spread widely and become a serious public health problem around the world. Membrane fusion inhibitor LP-98 shows strong antiviral activity among the anti-AIDS drugs under study in China, and has broad clinical application prospects. However, the clinical application of LP-98 is limited by its low solubility and poor suspension ability in aqueous phase, which could lead to blocked needle during injection and patient’s pain. To improve solubility of LP-98, high-pressure homogenization technology was used to prepare LP-98 nanosuspension lyophilized powder(LP-98 NSLP). The optimal preparation process was as follow: the optimum stabilizer was sodium dodecyl sulfate(SDS), the concentration of SDS was 0.80 wt%, the high-pressure homogenization pressure was 150 MPa, and it was repeated 5 times. The physical and chemical characterization and pharmacokinetics study of LP-98 NSLP were investigated. The LP-98 nanosuspension lyophilized powder had an average particle size of 261.5±1.1 nm and a Zeta potential of-31.5±0.2 m V. Circular dichroism spectrometer and single-cycle virus infection experiments showed that the structure and biological activity of active pharmaceutical ingredients(API) were unchanged. The pharmacokinetic results showed that the bioavailability of the LP-98 NSLP was 98.1% of API. The solubility of LP-98 in water has been increased from 184 μg/m L to 1733 μg/m L, which was 8 times higher than that of the API. The drug activity in the LP-98 nanosuspension lyophilized powder was well preserved, and the solubility of the drug was improved. As a result it solved the problem of blocked needle during injection due to poor suspension of LP-98, hence reduced patient’s pain. This research promoted the development of LP-98 application in clinical.
作者
张梦秋
靳惠娟
巩方玲
张佑红
韦祎
何玉先
马光辉
Mengqiu ZHANG;Huijuan JIN;Fangling GONG;Youhong ZHANG;Yi WEI;Yuxian HE;Guanghui MA(School of Environmental Ecology and Bioengineering,Wuhan Institute of Technology,Wuhan,Hubei 430205,China;State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China;MOH Key Laboratory of Systems Biology of Pathogens,Institute of Pathogen Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100190,China)
出处
《过程工程学报》
CAS
CSCD
北大核心
2021年第4期463-470,共8页
The Chinese Journal of Process Engineering
基金
国家重大科技专项(编号:2018ZX10301103-003)。
关键词
两亲性脂肽
纳米混悬液
高压均质法
溶解度
药代动力学
amphiphilic lipopeptide
nanosuspension
high-pressure homogenization
solubility
pharmacokinetics