Preparation Of Baicalin Loaded Solid Lipid Nanoparticles And Its Distribution In Vivo

Objective:Baicalin is often used to treat chronic hepatitis B in clinic and has great potential for development.In order to overcome the treatment dilemma of chronic hepatitis B,solid lipid nanoparticles which is easily absorbed by lymph system was used to deliver baicalin.Baicalin solid lipid nanoparticles was characterized,its physical and chemical properties were investigated,and its targeting ability was preliminarily explored.Methods:Solvent diffusion-low temperature curing method was used to prepare baicalin solid lipid nanoparticles solution.The optimum process and formulation by single factor and orthogonal test,taking entrapment efficiency,particle size and polydispersity coefficient as the evaluation indexes.The morphology and particle size distribution of baicalin solid lipid nanoparticles were observed by transmission electron microscopy and laser particle size analyzer.The drug release characteristics of baicalin solid lipid nanoparticles solution were investigated by in vitro dialysis.Freeze-drying protectant was added to the optimal formulation.The existence of baicalin in lyophilized powder baicalin solid lipid nanoparticles was investigated by differential scanning calorimetry,X-ray diffraction and Fourier transform infrared spectroscopy.The blood concentration and tissue distribution of baicalin solid lipid nanoparticles in mice were studied by using baicalin as reference material.To evaluate the targeting ability of baicalin solid lipid nanoparticles by targeting index,the relevant pharmacokinetic parameters were calculated.Results:The final prescription was baicalin 5.0 mg,glycerin monostearate 25.0 mg,cholesterol 25.0 mg,polyethylene glycol 40025.0 mg and phospholipid 50.0 mg.Baicalin solid lipid nanoparticles were spherical or ellipsoid under electron microscopy.The particle size,PDI and Zeta potential of baicalin solid lipid nanoparticles were 207±5.9 nm,0.134±0.011 and-35.4±7.5 mV,respectively.The in vitro release test showed that baicalin solution fitted well in the first-order release equation,while baicalin solid lipid nanoparticles solution fitted well in the Ritger-Peppas equation.Freeze-dried protective agent was added into baicalin solid lipid nanoparticles solution to make the powder dense and full in appearance.The freeze-dried powder was analyzed by differential scanning calorimetry,X-ray diffraction and Fourier transform infrared spectroscopy.It was found that lyophilized powder baicalin in baicalin solid lipid nanoparticles was dispersed in an amorphous state.Pharmacokinetic tests in mice showed that the AUC_0-t-t of baicalin solid lipid nanoparticles was 2.92 times higher than that of baicalin aqueous suspension.TI results showed that TI_spleen>TI_heart>TI_liver>TI_brain>TI_thymus>TI_kidney>TI_lung.TE results showed in baicalin suspension:TE_liver>TE_kidney>TE_brain>TE_lung>TE_spleen>TE_thymus>TE_heart,while TE results showed in baicalin solid lipid nanoparticles:TE_liver>TE_spleen>TE_brain>TE_kidney>TE_lung>TE_heart>TE_thymus.RTE in heart,liver,spleen,lung,kidney,brain and thymus were 52.48%,0.78%,84.32%,26.33%,23.76%,12.98%and 21.90%respectively.Conclusion:The encapsulation efficiency,particle size,PDI and Zeta potential of baicalin solid lipid nanoparticles solution prepared by solvent diffusion-cryogenic solidification method meet the stability requirements.In vitro release experiments prove that baicalin solid lipid nanoparticles have sustained release effect.Lyophilized powder of baicalin solid lipid nanoparticles were prepared by freeze-drying powder.Baicalin solid lipid nanoparticles can improve the absorption of baicalin in mice,and have a certain targeting to the spleen,liver and brain of mice.