Effect of ginkgolide B-loaded self microemulsifying drug deliver system on pharmacokinetics of ginkgolide B in retina / 中华实验眼科杂志

ABSTRACT

Background Ginkgolide B (GB) has been proved to have neuroprotective and anti-apoptotic effects and can effectively inhibit apoptosis of retinal photoreceptor cells.But the high hydrophobic feature and low bioavailability of GB limit its clinical application.Self microemulsifying drug delivery system (SMEDDS) can effectively improve the infusibility drug dissolution and bioavailability in the retina.Objective This study was to investigate the pharmacokinetics and drug-time change of GB-loaded SMEDDS in retina.Methods Eighty SD rats were randomized into 2 groups,2.5％ GB(40 mg/kg) of SMEDDS or GB suspension(0.1％ DMSO dissolve) were gastrically given respectively in two groups.The rats were sacrificed and retinas were isolated 15,30,45 minutes and 1 hour,2,4,8,12 hours to prepare the retinal suspension.The content of GB in retina was assayed with high performance liquid chromatography-electrospray ionization-(1) (1)ss spectrum (HPLC-ESI-MS) and contrasted with standard curve.Practical drug dynamics program 3p87 was used to detect the pharmacokinetics parameters.The maximal content(Cmax,mg/g),time to peak (Tmax,h),clearance ratio (Ke/h),high-life period (t1/2) and area under the concentration-time curve(AUC0-∞,mg/(g · h)) of GB in various time points in retina after a single oral dose were calculated and compared between two groups.Results The standard curve was obtained over the concentration range of 1-32 mg/L with a linear regression equation,Y =0.0732X + 0.056 (r =0.992).A similar content-time curve was seen between GB suspension group and GB-SMEDDS group.The GB content was higher in GB-SMEDDS group than that in GB suspension group from 30 minutes through 12 hours after administration of drugs.The Cmax of GB-SMEDDS group and GB suspension group were(15.83±1.84) mg/g and(2.65±0.10) mg/g,the AUC0-∞ were(15.30±0.11)mg/(g· h)and(6.42±0.19)mg/(g · h).Conclusions HPLC-ESI-MS is proved to be a rapid,accurate,sensitive and suitable method for pharmocokinetic study of GB.SMEDDS can raise the concent of GB in retina,and it probably improve the bioavailability of GB.