| It is well known that oral administration is the most widely applied in clinic researches. But there exists some particular drugs that would damage the activities of tissues if taken directly, such as COL. A resolution to this issue is to adopt the drug release technique of micro-delivery system, meanwhile, the technique has already become the main direction of the drug administration. So far, the materials to form drug delivery is various. The natural biodegradable materials have better biosecurity and biocompatibility than synthetic polymer materials among them. However, the deliveries made from the natural biodegradable materials have the disadvantages of releasing quickly through common processes of preparation. Sodium SAinate and chitosan are two kinds of polysaccharide which have huge reserves in the sea, and they both can be prepared to nontoxic ionic hydrogels while they have opposite electric property. The aims of this article are to improve the processes of making deliveries with no chemical cross-linking agent. And to achieve the controlled releasing.A novel kind of micro-delivery with sodium SAinate and chitosan was designed. The delivery is composed of two parts which are compact sodium SAinate submicro-spheres and chitosan micropheres. And the sodium SAinate submicro-spheres are equally distributed in the chitosan micropheres.The processes of sodium SAinate microparticles were improved through redesign of blender. As a result, the sodium SAinate submicro-spheres were well prepared. The novel blender could form circle floe field to make the system circular motive. Meanwhile, the drops would lose moisture through the program, and the concentration can raise from 2% to 21%. After the modified process, the dispersion coefficient decreased from 1.42 to 0.53, and the swelling degree decreased from 342.53±21.58% to 197.63±17.32%.Depending on the principle of focus current and circulation balling, the microfluid device was redesigned. That can remit the problems of blocking, rinsing and yield to a great extent. There are three factors such as internal flow, external flow and viscosity of aqueous phase which would affect the preparation. The internal flow can be 0.2mL/h to 4mL/h and the external flow lOmL/h to 80mL/h. Under the concentration of 6% chitosan, the particle size can be controlled, and the range of particle size from 25.1 μm to 231.4μm. After the parallel connection of the devises, the adding sample rate can increase from 2.74mL/h to 22.51mL/h. And here comes the regression equation of other parameters.The novel compound microparticles were combined sodium SAinate submicro-spheres and chitosan. The particle size of the mixture particles would increase with the amount of sodium SAinate submicro-spheres increasing. The particle size distribution is from 31.7μm to 201.4μm, coefficient of dispersion is inferior to 0.58±0.016, and the swelling degree is 187.21±11.63%. After the SEM, there is a compact TPP-CS-SA layer in the net structure. In the MTT test, there is no toxicity to HeLa cell line at the concentration of 0-500μg/mL. The TPP-CS-SA layer structure can reduce the swelling degree through a controlled test from 34.63±2.41% to 57.32±4.53%.Moreover, there are two methods of drug loading, and the drug-loading rate were 0.21% and 8.9%, which represent the direct method and immerse method. And the submicron microspheres were loading drugs through immersing COL, the highest loading rate can reach 1.27±0.14%. Then the content and particle size were the main factors in the investigation of drug releasing in simulated gastrointestinal fluids by dialysis. As a result, in the simulated gastric fluid, when the particle size of submicron microspheres increased from 3.17μm to 6.43μm, the cumulative drug release rate decreased from 18.50±2.51% to 14.34±1.32%. And when it comes to the simulated intestinal fluid, it decreased from 72.18±3.34% to 68.37±2.82%. It means that the particle size of submicron microspheres would reduce the release rate when it rises in the composite particles. Then with the volume of addition rising from 1% to 5%, its drug loading also increased from 0.092% to 0.57%. The rate in the simulated gastric fluid and simulated intestinal fluid were 27.72±2.51% to 19.07±1.32% and 83.21±3.41% to 74.42±1.72%, respectively. It means that even though the increasing of internal particles would enhance the loading rate of COL, but it would also increases the releasing rate. Then the concentration of chitosan was another main factor in the investigation of drug releasing in simulated gastrointestinal fluids by dialysis. The conclusion can be drawn that higher concentration of chitosan could not only rise the encapsulation rate, but also control the releasing rate. Cause the data in the simulated gastric fluid and simulated intestinal fluid are 57.17±2.51% to 19.07±1.32% and 89.42±3.41% to 74.39±1.72% while the encapsulation rate from 73.62% to 81.57% at the concentration of chitosan increased from 2% to 6%. Another analysis of composite micropheres and normal chitosan microspheres in the investigation of drug releasing in simulated gastrointestinal fluids by dialysis. It turned out that the releasing rate of composite microspheres and normal chitosan microspheres are 19.07±32% and 57.04±1.29% in the simulated gastric fluid, 89.42±2.12% and 74.13±2.07% in the simulated intestinal fluid. It means that the composite micropheres could remit the burst effect in the gastric acid environment to help the steadily controlled-release.In summary, after the improvement of the blender, the preparation of monodisperse and compact sodium SAinate submicro-spheres through emulsion. And with the optimizing of break-up of the droplet under the principle of focus current, a device of making chitosan microparticles faster, more stably and compactly was established. Then made a new type of composite microspheres with the combination of the two microparticles. The composite microshperes which are loading COL have better controllability than conventional microparticles in the simulated gastrointestinal fluids. And it would become a new research field in the area of COL drugs. |
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