Phospholipid-stabilized nanoparticles of cyclosporine a by rapid expansion from supercritical to aqueous solution
Phospholipid-stabilized nanoparticles of cyclosporine a by rapid expansion from supercritical to aqueous solution
复制标题
磷脂稳定的环孢素a纳米颗粒从超临界到水溶液快速膨胀
作者：
Timothy J. Young;K. Johnston;G. W. Pace;A. K. Mishra
本研究的目的是形成稳定的亚微米微粒环孢素A，水不溶性药物，从超临界快速膨胀到水溶液（RESAS）的悬浮液。将环孢霉素A在CO2中的溶液膨胀成含有磷脂囊泡的水溶液，所述磷脂囊泡与非离子表面活性剂混合，以提供对膨胀射流中碰撞引起的颗粒生长的稳定。通过用高效液相色谱法（HPLC）测量载药量、用动态光散射法（DLS）测量粒径、用透射电子显微镜（TEM）和X射线衍射测量颗粒形态来评价产物。表面活性剂分子在颗粒表面取向并提供空间稳定的能力可以通过改变工艺变量（包括温度和悬浮液浓度）来操纵。可以实现具有高有效载荷（高达54 mg/mL）的悬浮液，其平均直径为500 nm，粒度分布范围为40至920 nm。该尺寸范围比由RESAS产生的仅由吐温80稳定的颗粒小几百纳米。高的药物有效载荷（比平衡溶解度大10倍）、小的颗粒尺寸和长期稳定性使得该方法具有开发的吸引力。
The purpose of this research was to form stable suspensions of submicron particles of cyclosporine A, a water-insoluble drug, by rapid expansion from supercritical to aqueous solution (RESAS). A solution of cyclosporine A in CO2 was expanded into an aqueous solution containing phospholipid vesicles mixed with nonionic surfactants to provide stabilization against particle growth resulting from collisions in the expanding jet. The products were evaluated by measuring drug loading with high performance liquid chromatography (HPLC), particle sizing by dynamic light scattering (DLS), and particle morphology by transmission electron microscopy (TEM) and x-ray diffraction. The ability of the surfactant molecules to orient at the surface of the particles and provide steric stabilization could be manipulated by changing process variables including temperature and suspension concentration. Suspensions with high payloads (up to 54 mg/mL) could be achieved with a mean diameter of 500 nm and particle size distribution ranging from 40 to 920 nm. This size range is several hundred nanometers smaller than that produced by RESAS for particles stabilized by Tween 80 alone. The high drug payloads (≈10 times greater than the equilibrium solubility), the small particle sizes, and the long-term stability make this process attractive for development.