Oral Delivery Of Insulin Via Mesoporous Carbon Nanoparticles For Colonic Release Allows Glycemic Control In Diabetic Rats

In this article,a new type of mesoporous carbon nanoparticles(MCN)was fabricated as a potential oral delivery system of insulin to reduce the adverse reactions by hypodermic injection.1.The preliminary evaluation of oral polypeptides preparation based on mesoporous carbonsMesoporous carbons were prepared and were used to treat with the polypeptides FITC-QQMHLMSYAPGP(FQ for short,the same below)which is marked with fluorescence.The polypeptides treated with mesoporous carbons were given into nude mice with cancer A549,and the absorption and distribution of the polypeptides was shown.It intends to solve the oral administration of polypeptides.Mesoporous carbons were prepared by glucose and silicon dioxide with dissolution,high-temperature calcinations and abstersion.Nude mice were divided in the control group,intravenous injection group,oral administration group with mesoporous carbons and oral administration group without mesoporous carbons.10 minutes after administration in different ways,nude mice were narcotized and dissected.Hearts,livers,spleens,lungs,kidneys,brains and cancers were taken out,fixed by 10% formaldehyde in 2 h,dehydrated by 40% sucrose in 2 h and make frozen sections.Frozen sections were detected by fluorescence microscopic photography to infer that the distribution of the polypeptides FQ in these organs.10 minutes after oral administration of the polypeptides FQ treated with mesoporous carbons,the sections of liver and heart in nude mice with cancer showed green fluorescence,but those could not show green fluorescence without mesoporous carbons,.It showed that the polypeptides FQ treated with mesoporous carbons could be absorbed by oral administration and distributed in liver and heart.It provided a good excipient for oral administration,and a good basic for development of oral polypeptides preparations.2.Oral delivery of insulin via mesoporous carbon nanoparticles for colonic release allows glycemic control in diabetic ratsIn this drug delivery system,three different kinds of mesoporous carbons with different properties were compared as drug carriers for the oral delivery system of insulin.Insulin was loaded onto mesoporous carbon nanoparticles by stirring and evaporating.The mesoporous carbons nanoparticles carried insulin(MCNI)were studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM)and Fourier transform infrared spectroscopy(FT-IR)compared with the blank MCNs.The Brunauer-Emmett-Teller(BET)method was utilized to calculate the specific surface area.The pore volume and pore size distribution(PSD)curves were calculated by Barrett-Joyner-Halenda(BJH)model.The entrapment efficiency(EE%)and loading content(LC%)of insulin onto the MCNs were determined by HPLC.In order to study the insulin release from MCNI to gastrointestinal tract,In vitro insulin release from MCNI was determined in simulated intestinal fluid.To evaluate the pharmacodynamics of MCNIs orally,the variation of glycemia of diabetic rats after oral administration of MCNIs was compared with the rats receiving hypodermic injection of insulin.Besides,the absorption of FITC-labeled MCNs in HCT-116 cells was tested.The results showed that there is significant difference between MCNs and MCNIs through SEM and TEM.The FT-IR spectrums showed the spectral absorption peaks of insulin among the MCNIs.The entrapment efficiency of insulin onto MCN-1,MCN-2 and MCN-3 is 41.52%±1.99%,28.77%±0.30% and 49.49%±1.78%,respectively.The loading content of MCNI-1,MCNI-2 and MCNI-3 was 12.16%±0.51%,8.68%±0.08% and 14.06%±0.43% respectively,which met the requirements of the pharmacodynamic study.The specific surface area,pore volume and pore size of MCNIs were significantly decreased compared to that of MCNs.In vitro insulin release from MCNI-1,MCNI-2 and MCNI-3 to p H7.4 PBS would be reached at 48.20%±8.93%,15.68%±5.50% and 53.11%±3.69% in 15 minutes.The pharmacodynamics study showed that the blood sugar level was significantly decreased during the 4-hour duration after the oral administration of MCNIs,which showed the effect of sustained drug release compared with hypodermic injection.The FITC-labeled MCNs showed significant absorption in HCT-116 cells and it provided a base for investigating the mechanism of MCNI transportation in the gastrointestinal tract.In summary,The MCNIs were successfully synthesized with commendable entrapment efficiency and loading content which preferably decreased the blood sugar in diabetes rats via oral administration and provided a base for the research & development of oral insulin agentia.