The Preparation Of Nano-Drug-Encapsulation Microbeads By Microfluidic Method For Liver Cancer Chemoembolization

The mortality of Hepatocellular Carcinoma(HCC)is the second high in cancer.Hepatocellular Carcinoma malignant degree is so high that this cancer has usually been unable to perform surgery at the time of diagnosis in patients.A minimally invasive interventional method,Transcatheter Arterial Chemoembolization(TACE),is the most promising treatment dealing with hepatocellular carcinoma and postoperative recurrence of liver cancer.The interventional therapy TACE combines chemotherapy drugs with embolization agents to block the blood supply of the tumor and concentrate the chemotherapy drug on the tumor site.Embolism microsphere is a hot spot,but the preparation methods are difficult to control the size of microspheres.At the same time,the effective availability of nano-medicine in human tests is very low.In order to solve these two problems,we are trying to use the microfluidic chip to produce the uniform and controllable particle size of microspheres containing nano-medicine.By combining the microspheres of interventional therapy and nano-medicine,we try to improve the utilization rate of nano medicine at well as block the blood supply of the tumor.In the experiment,a set of microfluidic device was set up to generate the micro droplet,and the temperature control system was established for the dispersion-phase gelatin solution.In the case of fixed continuous phase velocity,we designed the four factors(dispersed phase velocity,concentration of surfactant,concentration and temperature of gelatin solution)three levels orthogonal experiment.By this experiment,we found the surfactant concentration and dispersed phase viscosity are very important to generate the micro droplet.The relationship between the size and velocity of microspheres is determined by changing the velocity of the dispersed phase.In the process of the crosslinking of microspheres,we transfer gelatin microspheres into water to be cross linked by genipin.Hydrogel microspheres which contain nano-medicine were prepared under the guidance of the preparation of the gelatin microspheres.Experimental results show that this established temperature control method of T—junction microfluidic chip in the preparation of embolism gelatin microsphere has huge advantages:it can produce monodisperse,controllable microsphere containing nano-medicine;under the action of enzyme degradation,it gradually forms the blood vessel recanalization which allows secondary embolization.The microspheres of embolism are in the category of interventional instruments and have certain requirements for their biocompatibility.By the testing of hemolysis ratio,plasma recalcification time and cytotoxicity,we prove that this kind of interventional embolization microsphere meets the requirements of biometric intervention equipment,and have no toxic effect for normal cells.We worked with the hospital on animal testing after proving that the microspheres met the requirements for intervention.After two weeks of preparing the VX2 liver cancer model of the rabbit,the treatment of embolization was made with our nano-drug-loaded hydrogel microspheres of 65-70 microns.Preliminary results confirmed that the embolization effect of this type of embolization was good,and the blood vessels of the tumor were fully embolized.The above experiment results show that using microfluidics to prepare nano-drug-loaded interventional embolization microspheres is promising due to the uniform and controllable particle size,biodegradability and improvement of the utilization nano-medicine.Its interventional embolization for the treatment of liver cancer has great potential.