两亲性脂肽纳米混悬液冻干粉的制备及其表征

Preparation and characterization of amphiphilic lipopeptide nanosuspension lyophilized powder

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.