Study On Preparation And Kidney Penetration Of Rhein Nanoparticles

Objective To prepare rhein-loaded polyethylene glycol-polylactic acid nanoparticles(RH-PEG-PLA-NPs),and investigate their physicochemical properties,in vitro release behavior and in vivo pharmacokinetics.Methods RH-PEG-PLA-NPs were prepared by emulsification solvent evaporation method with PEG-PLA as a carrier material.Single factor investigation was used to optimize the preparation procedure.Mean particle size and Zeta potential were estimated by laser particle size analyzer.Morphology of RH-PEG-PLA-NPs was observed by transmission electronmicroscope.Entrapment efficiency and drug loading were investigated by ultrafiltration method.Drug release behavior in vitro was studied by dialysis method.The plasma-kidney pharmacokinetics behavior of RH-PEG-PLA-NPs were studied simultaneously after vein administration in comparison with RH.Moreover,the kidney penetration of RH-PEG-PLA-NPs was evaluated.Results The morphology of RH-PEG-PLA-NPs was spherical.The mean particle size,Zeta potential were(132.6±5.95)nm and(0.035±0.01)mv respectively.Entrapment efficiency and drug loading were(62.71±3.02)%and(1.56±0.15)%respectively.The release behavior in vitro showed a significant sustained characteristics.The AUC in plasma and kidney were(354.27±79.78)and(147.56±11.90)ng·h/mL after vein administration of RH in rats,it's kidney penetration was(0.41±0.02).The AUC in plasma and kidney were(629.15124.57)and(337.27±25.83)ng-h/mL after vein administration of RH-PEG-PLA-NPs in rats,it's kidney penetration was(0.52±0.03).The results showed that RH-PEG-PLA-NPs can penetrate the rat's kidney well,thereby increasing its concentration in kidney to exert its efficient in kidney disease treatment.Conclusion The RH-PEG-PLA-NPs prepared by ESE method were smooth and round with well-distributed particle size as well as high entrapment efficiency and drug loading.The release behavior in vitro showed significant sustained release characteristics.Compared to RH,RH-PEG-PLA-NPs can prolonged retention time in the kidney.The difference of kidney penetration between RH and RH-PEG-PLA-NPs is significant,the results confirmed RH-PEG-PLA-NPs can easily penetrate to kidney,maintain a high concentration for a long time to develop the therapeutic effect of RH.