西那普肽脂质体气溶胶体外评价

In vitro Evaluation of Sinapultide Liposomal Aerosols

制备并评价了西那普肽脂质体。冻干前后脂质体的平均粒径、ζ电位和包封率分别为556.5和651.2 nm、-56.8和-41.6mV、83.8%和70.4%。冻干脂质体中残余水分含量为1.48%,氯仿和甲醇的残留量低于中国药典2015年版的限度要求。利用Pari雾化器将用生理盐水复溶后的西那普肽脂质体雾化,形成气溶胶,再分别采用双级撞击器、新一代撞击器(next generation impactor,NGI)、飞行时间(time-of-flight,TOF)空气动力学粒径谱仪对气溶胶的体外沉积性质进行考察。结果表明,双级撞击器、NGI和TOF测得的体外沉积性质相似;双级撞击器和NGI测得空气动力学粒径小于6.4 um的脂质体气溶胶中的西那普肽含量占总药量的比例为50.86%和43.87%,NGI和TOF测得的空气动力学质量中位径(mass median aerodynamic diameter,MMAD)值为3.09和2.81 um。这些结果提示西那普肽脂质体气溶胶能够在肺部沉积,具有较好的开发应用前景。

The sinapultide liposomes were prepared and then lyophilized. The average particle size, ζ potential and encapsulation efficiency of the original liposomes were 556.5 nm, -56.8 mV and 83.8%, respectively; while the above indexes of the reconstituted lyophilized liposomes were 651.2 nm, -41.6 mV and 70.4%, respectively. The average residual water of the lyophilized liposomes was 1.48%. The residual amounts of trichloromethane and methanol were below their corresponding limits in the 2015 edition of Chinese pharmacopoeia. After reconstitution by adding normal saline, the aerosols were obtained by nebulizing the sinapultide liposomes with Pari nebulizer. The deposition properties of the aerosols in vitro were determined by twin-stage impinger, next generation impactor （NGI） and time-of-flight （TOF）, and the results had no significant differences. The drug amounts in the aerosols with the aerodynamic particle size smaller than 6.4 μm were 50.86% measured by twin-stage impinger, and 43.87% measured by NGI. The values of the mass median aerodynamic diameter （MMAD） were 3.09 μm measured by NGI, and 2.81 μm measured by TOF. All the results of the in vitro evaluation suggested that the nebulized sinapultide liposomal aerosol enjoyed effective pulmonary deposition and provided a promising future of development and application.