Study On Nanoparticle Drug Delivery System Of Taxifolin

Taxifolin is widely distributed in many Chinese herbs, such as the rhizome of Smilax glabra, a Liliaceae plant and Hypericum perforatum, also have been found in many citrus fruits, especially grapefruit and orange. It has been reported that taxifolin has many activities in anti-bacteria, anti-oxidative, anti-inflammation, anti-cancer, as well as hepato-protection. However, Taxifolin has poor water-solubility and low bioavailability for oral administration due to slow drug dissolution and decomposition in the stomach and intestine. Therefore, the development of the new formulation of Taxifolin that enables quick availability to the body is in great need. In this study, solid lipid nanoparticles (SLN) and liposomes of Taxifolin were prepared.Taxifolin liposomes and solid lipid nanoparticles(DHQ-SLN) were prepared by solvent injection method. Central composite design-response surface methods were used to obtain the optimum prescription of SLN. The single factor experiment results were applied to have taxifolin liposomes. Three batches of DHQ-SLN were prepared using the optimized formulation. From the transmission electron microscope observation, the nanoparticles were spherically shaped, the encapsulation efficiency was 80.9±3.5%, and drug loaded capacity was 13.9±2.0%, the average diameter was 125.0±1.5nm, zeta potential was -24.3±6.1mv. The liposomes with spherical or ellipsoidal shape featured the encapsulation efficiency of 68.1±4.5%, the mean partical size of 166.4±2.9 nm, and Zeta potential of -32.3±4.9mV.An HPLC method was developed for the detemination of taxifolin in mice plasma. Intravenous pharmacokinetic behaviors of taxifolin solution, taxifolin liposomes and DHQ-SLN suspension were investigated in mice. The plasma concentration-time profiles of taxifolin were fitted to the three compartment model. The plasma pharmacokinetic parameters were obtained as following(n=3):solution:AUC(0-∞) 15.745mg/L*h, t1/2β0.021h, Cmax 31.02mg/l, Tmax 0.083h, CL 3.176L/h/kg; liposomes:AUC(0-∞) 20.962mg/L*h, t1/2β0.279h, Cmax 15.30mg/l, Tmax 0.083h,CL 2.385L/h/kg; DHQ-SLN:AUC(0-∞) 17.61mg/L*h, t1/2β0.116h, Cmax 18.60mg/l, Tmax 0.083h, CL 2.839L/h/kg. The results showed that the AUC(0-∞) of taxifolin liposomes and DHQ-SLN were higher than that of solution, and less elimination. Solution, liposome, nanoparticle group Cmax were:31.02mg/l,15.30 mg/l,18.60 mg/l, showed the distribution of solution in the body faster than the other two preparations.