Studies On Preparations And Drug Releasing Properties Of Drug-loading Microcapsules Of Double Compositions Of Chitosan-Sodium Alginate And Chitosan-Sodium Carboxymethyl Cellulose

according to the principle of macromolecule self-assemble, chitosan(CS)-sodium ,alginate (SALG) microcapsules and CS-sodium carboxymethyl cellulose (SCMC) microcapsules used for injection were prepared in emulation by using glutaraclelhyge (GA) or epichlorohydri(ECH) as cross-linking agent to encapsulelow molecular weight heparin (LMWH) . The properties of the microcapsules were characterized by IR,UV-VIS,SEM and particle size analysis. The drug-releasing performances of the microcapsules were investigated by release-in- vitro tests andanimal experiment. A series of studies and results is follows:l)The microcapsular cores of LMWH were prepared by being dispersed in emulsion and then were encapsulated with CS and were further encapsulated with SALG by means of macromolecular self-assemblage to form complex microcapsulesof multi-layer structure. The IR results indicated that there was a strong electrostatic interaction between LMWH and CS and between CS and SALG. SEM images showed the LMWH/CS/SALG microcapsules are spherical shape with an average diameter of <5//m. The greatest LMWH-encapsulated capacity reached to 93.5%. The results of the experiments to test the drug-releasing performance of the microcapsules showed that the half-releasing time of the LMWH in microcapsules reached to 72h . With decrease of the concentration of CS or SALG, the LMWH-releasing rate would increase; the higher the mass ratio of LMWH to CS, the slower the drug-releasing rate of the microcapsules; high cross-linking degree could result in a good drug-slow-releasing performance; and the drug would release slightly faster in acid media than in alkali one.2)LMWH/CS/SCMC microcapsules were prepared by means of emulation using GA or ECH as cross-linking agent. The spherical microcapsules with an average diameter of <5m were obtained. The drug-loading rate and the drug-encapsulated capacity of the microcapsules using ECH as cross-linking agentwere higher than those using GA as cross-linking agent. With the increase of CS or SCMC concentration , and the decrease of the mass ratio of LMWH to CS, the LMWH -releasing rate would decrease, and it was showed that drug-releasing rate of the microcapsules was dependent on pH value of the media ; that using ECH as cross-linking agent resulted in a better drug-releasing performance than using GA. The animal experiment result showed a significant sustained release effect of the microcapsules.3) SALG/CS/ microcapsules with an average diameter of <5m were prepared by means of emulation using CaCl2, GA, ECH and CaCl2+GA, CaCl2+ECH as cross-linking agent. The microcapsules using two kinds of cross-linking agent havebetter spherical shape and with higher drug-encapsulated capacity. With increase of the concentration of CS or SALG, the LMWH-releasing rate would decrease; the lower the mass ratio of LMWH to SALG, the slower the drug-releasing rate of themicrocapsules; the drug-releasing rate would go down in proper with using GA , CaCl2,ECH,CaCl2 +GA,CaCl2 +ECH as cross-linking agent; and that drug-releasingrate of the microcapsules were dependent on the pH value of the media.4) SCMC/CS microcapsules were prepared by means of emulation using GA,ECH as cross-linking agent. The microcapsules were showed under SEM and analyzed by laser size analyzer, which showed that the microcapsules were characteristic with spherical shape, slippery surface and the diameters range from 1-7 m. With increase of the concentration of CS or the swelling rate and thedrug-releasing rate would raise; the swelling rate and the drug-releasing rate would go down in proper with not cross-linking, using GA, using ECH as cross-linking agent respectively; the higher the SCMC concentration , the slower the drug-releasing rate and the greater the swelling rate of the microcapsules.