Preparation and in vivo Pharmacokinetics in Rats of Nimodipine Nanostructured Lipid Carries

Abstract:

Objective: To prepare nanostructured lipid carriers modified with mPEG₂₀₀₀-DSPE(mPEG2000-DSPE-NMD-NLC) and investigate its properties and in vivo pharmacokinetics in rats. Method: mPEG2000-DSPE-NMD-NLC were prepared by melt ultrasonication method,morphology was observed by TEM,particle size,entrapment efficiency,drug loading and Zeta potential were determined,in vitro release was examined.Plasma concentrations of nimodipine at different time point in rats were determined by HPLC,with nimodipine injection as control,pharmacokinetics parameters of mPEG2000-DSPE-NMD-NLC in rats were calculated. Result: Prepared mPEG2000-DSPE-NMD-NLC showed spherical with uniform size and rounded surface;Particle size was about 85 nm,Zeta potential was (-12.77±0.15) mV,entrapment efficiency and drug loading were (97.66±0.45)% and (3.36±1.53)%,respectively;Cumulative release of mPEG2000-DSPE-NMD-NLC was 20.03% within 0-6 h,and 43.06% at 24 h.Pharmacokinetic parameters were as follows:t1/2=21.65 h,MRT=21.09 h,CL=557.30 mL·h^-1·kg^-1,AUC_(0-t)=6 411.96 μg·h²·L^-1. Conclusion: Particle size distribution of mPEG2000-DSPE-NMD-NLC was uniform,its showed obvious in vitro and in vivo sustained-release characteristic.This study could lay foundation for improving clinical efficacy of nimodipine.