欢迎访问过程工程学报, 今天是

过程工程学报 ›› 2021, Vol. 21 ›› Issue (4): 463-470.DOI: 10.12034/j.issn.1009-606X.220144

• 生化工程 • 上一篇    下一篇

两亲性脂肽纳米混悬液冻干粉的制备及其表征

张梦秋1,靳惠娟2,巩方玲2,张佑红1*,韦祎2*,何玉先3,马光辉2   

  1. 1. 武汉工程大学环境生态与生物工程学院,湖北 武汉 430205 2. 中国科学院过程工程研究所生化工程国家重点实验室,北京 100190 3. 中国医学科学院北京协和医学院病原生物学研究所,卫生部病原体系统生物学教育部重点实验室,北京 100190
  • 收稿日期:2020-04-30 修回日期:2020-05-27 出版日期:2021-04-22 发布日期:2021-04-28
  • 通讯作者: 张佑红
  • 基金资助:
    艾滋病和病毒性肝炎等重大传染病防治科技重大专项

Preparation and characterization of amphiphilic lipopeptide nanosuspension lyophilized powder

Mengqiu ZHANG1, Huijuan JIN2, Fangling GONG2, Youhong ZHANG1*, Yi WEI2*, Yuxian HE3, Guanghui MA2   

  1. 1. School of Environmental Ecology and Bioengineering, Wuhan Institute of Technology, Wuhan, Hubei 430205, China 2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China 3. 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
  • Received:2020-04-30 Revised:2020-05-27 Online:2021-04-22 Published:2021-04-28
  • Contact: You-Hong -ZHANG

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 mV。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184 μg/mL提升至1733 μg/mL,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。

Abstract: 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 0.80wt%, 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 mV. 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/mL to 1733 μg/mL, 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.