The Study On The Construction Of Drug-loaded NanoMOFs System

Metal-Organic Frameworks (MOFs) are new porous organic-inorganic hybrid functional materials. Compared with the classical inorganic microporous material, MOFs have rich spatial and topological structure,higher specific surf-ace area and unique electromagnetic properties. In this study,5-FU which are the representative drug in the antitumor diseases was encapsulated in nanoporous metal-organic framework to explore the feasibility and laws of the nanoporous metal-organic framework as a carrier.Firstly,we investigate the preparation of Cu-BTC. The particle size,morphology and dispersibility were as indicators, to detect the influencing factors of solvothermal method and coordination modulation method respectively using single factor method.The results shows that coordination modulation method can prepare nanostructure particles with good dispersity. Then orthogonal design was used to optimize the best condition of reactant concentration,strring rate.titration time, which shows that the optimized conditions were C2(copper acetate 0.3g, beenzoic acid 4g,Benzenetricarboxylic acid 0.8g),1.5h and 1000 r/min. Based on all the results from the tests concerned, the best preparation process was that first we dissolved CuAC2 (0.36g) and C6H5COOH (modulator, 4g) in 30 mL normal butyl alcohol. H3BTC (0.8g) was dissolved in 30 mL DMF and stirred. Next.H3BTC was added dropwise to a metal salt solution (CuAc2)slowly at room temperature over a period of 30 min. The solution was stirred for 30 min. The resultant NMOFs were recovered by centrifugation and solvent was removed along with residual non-reacted organic acids via washing twice in ethanol.The products were characterized by powder XRD which demonstrated that they had the similar X-ray diffraction patterns as the standard patterns which was simulated from the single crystal structure.SEM and DLS was used to view the morphology of carriers and particle size distribution. The results of SEM shows that the particle size was 50?100nm, but the DLS results shows that it was about 270nm. This was due to many water molecules gathered around the carriers which enlarged the diameter of carriers when they dissolved into water. Besides, from the SEM map we can see the morphology of carriers was structured round, non-sticky and has good distribution. The pore of carriers was characterized by TEM and nitrogen adsorption instrument. The results showed that the pore of carriers was 2?5nm,which was suitable for loading the drug of which particle size was less than it. Finally, we study the hemolytic characteristics of carriers. The experimental results proved that the carriers had good blood compatibility and was suitable for drug loading.Response surface method was used to optimise the best drug loading technology. Firstly, drug loading capacity was as indicators, to detect the optimal district of levels of many influence factors by means of the single factor experiment. It turned out that the bigger influences on drug loading were the 5-FU/material ratio, contacting time and ethanol concentration. So we used them as independent variables and investigate the optimal drug loading technology by response surface method. The results indicated that the best results were achieved when 70% ethanol, 7:1 the 5-FU/material ratio and 96h contact time. Under the optimum conditions, the optimised drug loading was above 30% and the technology was stable easy to handle and the results was reliable.The study of characteristic on drug loading MOFs was taken. The result of SEM showed that the morphology of carriers had no obvious changes before and after drug loading, which means the prosess of drug loading had no effect on the morphology of carriers. The result of wide angle XRD showed that the graphs of before and after drug loading had no distinct different. Small-angle diffraction showed that the pore of carriers had changed after drug loading, which proved drug had loaded into the pore of carriers. Release in vitro experiment was done by means of comparing the results of DM and RDM. Zero-order equation, one equation, Higuchi equation was used to fit the release behavior to study release degree in vitro.The results showed that in vitro release profile of the datas from two methods consistent with one equation without exception, and they all revealed burst release in the first 1 hour. This was caused by the drug absorbed on the surface of carriers spreaded into the dissolve medium and then released smoothly.In vitro cytotoxicity studies of drug loading MOFs was made by MTT method. Results indicated that blank carriers has the same cytotoxicity as 5-FU, and 5-FU-CU-BTC has higher toxicity. From cellular uptake studies of FITC-5-FU-CU-BTC measured by Inverted flurescence microscopy, we can see that FITC-5-FU-CU-BTC can be taken by cells, and the amount of carriers taken by cells was increased with the sample concentration increased.The results of FCM showed that the process of cellular uptaken presented saturability and temperature dependency. It was speculated preliminary that the cellular uptaking process of FITC-5-FU-CU-BTC gone through endocytic pathways.