Preparation Of Alginate/Poly-L-Arginine-Chitosan Complex Microcapsules

According to the polyelectrolytical complex reaction, the calcium alginate beads produced by using high-voltage electrostatic droplet generator were coated with poly-L-arginine and chitosan as membrane materials to prepare the alginate/poly-i-arginine-chitosan complex microcapsules. The factors which affect the properties of beads or alginate/poly-L-arginine-chitosan complex microcapsules were investigated.Firstly, the calcium alginate beads were produced by using high-voltage electrostatic droplet generator, the influences on beads profiles such as concentration of sodium alginate solution, voltage, push speed and pinhead were studied to select the basic parameters to produce microcapsules. The optimum operating parameters were: concentration of sodium alginate solution 1.8% (w/v), voltage 9.5*2/3 kv, push speed 50 mm/h, distance between the pinhead and the surface of CaCl2 solution 20 mm, 5# flat pinhead, 10mL syringe. And the beads resulted had good spherical degree, smooth surface and narrow particle distribution, the diameter of beads could be controlled within 200 m~500 m.Secondly, the microcapsules were prepared according to the polyelectrolytical complex reaction between poly-L-arginine, chitosan and alginate. The facts which affected the properties of the microcapsules, such as chitosan molecular weight, chitosan concentration, drug loading methods, membrane-forming materials, membrane-forming ways, membrane-forming time and additive were investigated. While combining mixing and adsorption to load drug, using mixture of poly-L-arginine and chitosan to form membrane for 10 minutes, the alginate/poly-L-arginine-chitosan complex microcapsules resulted had higher drug load, encapsulation efficiency and good controlled release properties.Finally, the drug release kinetics of alginate/ poly-L-arginine-chitosan complex microcapsules were investigated by using bovine hemoglobin (Hb) as a macromolecular drug model and 5-Flucrouracil (5-Fu) as a low molecular drug model.It was found that release of Hb was almost in a first-order kinetics process(r=0.98315, MSE=0.19743), the accumulative total of Hb released was 8.12% in half hour, and reached 95.1% in 46 hours, it demonstrated that there's no burst effect and the drug would release completely in a stable way, the complex microcapsules had a good controlled release efficacy for macromolecular drug; whereas the accumulative total of 5-Fu released from the alginate/poly-L-arginine-chitosan complex microcapsules prepared by using the combination of one-step method and two-step method was 33.0% in half hour which there's a burst effect, then the release speed turned to be stable in 10 hours, then the release turned to be retarded, the accumulative total of 5-Fu released was 83.5% in 35 hours, however it demonstrated that the complex microcapsules had a controlled release properties for low molecular drug in a certain extent. In addition, the pH stimuli-response characteristics of complex microcapsules were also investigated. It found that Hb was hardly to release from complex microcapsules in pH 1.0 HC1 solution, whereas it released sustainedly and stablely in the pH 6.8 phosphate buffer solution, the complex microcapsules were potential to be an ideal protein drug carrier with a targeted delivery to the intestine.