维甲酸纳米颗粒混悬剂的制备及对实验性增殖性玻璃体视网膜病变的预防作用

Preparing retinoic acid nanosuspensions and preventing experimental proliferative vitreoretinopathy

目的:制备维甲酸药物的纳米颗粒混悬剂,并探讨其对兔眼实验性增殖性玻璃体视网膜病变(PVR)的预防作用。方法:采用溶剂分散法制备了维甲酸纳米颗粒混悬剂并对制备条件及配方进行了优化;对维甲酸纳米颗粒混悬剂进行了冷冻干燥;用光子相关光谱(PCS)测定了冷冻干燥前后混悬剂中纳米粒子的平均粒径;透射电镜(TEM)观察其微观形貌;建立了兔眼PVR模型,并考察了维甲酸纳米颗粒混悬剂对PVR的预防作用。结果:混悬剂中维甲酸纳米粒子(RA-NP)的粒径保持在300～400nm之间,大都为完整的球形;PVR预防实验显示,在术后28天,用药组的视网膜脱离发生率较对照组明显减少,且有统计学差异(χ2=19.798,P<0.01),表明维甲酸纳米颗粒混悬剂能够有效的预防PVR的发生。结论:维甲酸纳米颗粒混悬剂有望成为一种新型的PVR治疗用药物载体。

Objective：To prepare retinoic acid （RA） nanosuspensions and to evaluate the ability of RA nanosuspensions to prevent the proliferative vitreoretinapathy （PVR）. Methods：RA nanosuspensions were prepared by solvent-diffusion method in aqueous and freeze-drying. The mean particle size before and after drying was determined by photon correlation spectroscopy （PCS） method and the morphology of RA nanoparticles（RA-NP）was observed by transmission electron microscope（TEM）. The PVR model on rabbit eyes was founded and the ability of RA nanosuspensions to prevent the proliferative vitreoretinapathy was evaluated.Results： RA-NP in the nanosuspensions were unequal spherical nanopartilces with average size of 300-400 nm, and with polydipersity index less than 0.5. The incidence of retinal detachment （RD） in control group was 90% while that in ATRA nanosuspension group was only 20%. Twenty-eight days after the surgery, 20 （100%） eyes of control group and 13 （75%） of ATRA group occurred vitreous proliferation. Conclusion：RA nanosuspensions may be used as a promising DDS for the PVR.