The Preparation,Characterization And Bioavailability Of Melatonin@ Mesoporous Silica Enteric Nanoparticles

Melatonin(MLT)is a natural product synthesized by the pineal gland of mammals,it plays an important role in various physiological processes.Melatonin is a small molecule with low water solubility and high permeability.According to the Biopharmaceutics Classification System,MLT is a class ? drug exhibiting a very short half-life and minimal and variable bioavailability.Therefore,this article use nano-silicon dioxide(SiO2)load melatonin and coated by enteric material(HP55),get a MLT-SiO2-HP55 nanometer powder.Compared with raw melatonin has controlled and sustained release characteristics,not only improve the solubility and dissolution of melatonin,and significantly higher bioavailability.This research work and results are as follows:(1)The melatonin concentration gradient experiment was investigated according to the maximum solubility of melatonin in different solvents,the results show that with the melatonin concentrations increased,the drug loading of silica increased,and the drug loading show a good linear relationship between concentration of melatonin and silica,Langmuir and Freundlich equation for drug concentration proved that silica adsorption was physical with strong adsorption ability.(2)The drug concentration of 40 mg/mL,the concentration of silica at 55 mg/mL,adsorption temperature at 25?,adsorption was 10 min,speed was 1400 r/min were selected as the optimal conditions in the process of nano silica adsorption of melatonin,under the optimal conditions of preparation of MLT-SiO2 nanospheres,the drug loading of silica is 24.73%.(3)HP55 was not easily dissolved in water,but could be dissolved in acetone solution,so this article applies the liquid antisolvent precipitation method to prepare MLT-SiO2-HP55 nanoshperes,acetone solution as solvent,the anti-solvent was water,PVA as binder.The gradient experiments of HP55 in MLT-SiO2-HP55 were investigated to get MLT-SiO2-HP55(with HP55 content of 3.28%,7.89%and 15.41%),respectively.(4)The MLT-SiO2-HP55 obtained was characterized by Transmission electron microscope(TEM),(BET),Fourier-transform infrared(FT-IR),Differential scanning calorimetry(DSC),thermogravimetric analysis(TGA)and X-ray diffraction(XRD),the results indicated that the silica nanosphere were relatively smooth with a lot of pore on the surface,most of the pore of silica were filled and the surface become rough after the load of melatonin,the specifie surface area smaller after HP55 was wrapped on the surface of silica,most of the melatonin was loaded in the pore of silica,small amount of melatonin was loaded on the surface of silica,melatonin in MLT-SiO2 and MLT-SiO2-HP55 was amorphous.Gas chromatographic detected acetone content in the MLT-SiO2-HP55 powder,the content is far lower than the ICH limits of ? kind of organic solvent,MLT-SiO2-HP55 powder suitable for pharmaceutical standards,antioxidant capacity of melatonin loaded by silica significantly better than the original melatonin,and with the increase of the content of coating material HP55 melatonin loaded by silica showed the antioxidant capacity of gradually strengthen than the original melatonin in vitro antioxidant eapacity measurement.(5)The release characteristics of MLT-SiO2-HP55 in the simulated gastric fluid(SGF,pH 1.2)and simulated intestinal fluid(SIF,pH 7.4)was evaluated,the results show that the silica load melatonin increased the release rate of melatonin in SGF and SIF,the release rate of MLT from MLT-SiO2-HP55 in SIF was higher than that of in(SGF).The cumulative release rates of MLT,MLT-SiO2 and MLT-SiO2-HP55(with HP55 content of 3.28%,7.89%and 15.41%)in SIF were 0.80,0.91,1.14?1.50 and 2.47 times higher than that of SGF.The absorption of silica enhanced the solubility,dissolution rate of MLT and MLT-SiO2-HP55(with HP55 content of 15.41%)was effectively used for the oral administration.(6)The bioavailability of MLT-SiO2-HP55 in rats was evaluated.Compared with raw MLT,MLT-SiO2 prolonged Tmax from 15 min to 30 min and increased Cmax from 168.86 ng/mL to 383.71 ng/mL.The corresponding AUC of MLT-SiO2-HP55 was 3.5 times of raw MLT.Elimination half-life t1/2 from 22 min extended to 57 min.This finding illustrated the sustained release of MLT-SiO2-HP55.