Fabrication And Property Of Azido-Chitosan And Its Ionic Gelation Particles

Chitosan is a renewable resource of outstanding biological compatibility anddegradability, particularly protonated property. However, most of adopted modifications tochitosan have improved chitosan property with the protonation property weakened.Modification at C6-OH with azido group, instead of C2-NH2, has showed effective prospectsto endow chitosan with novel effective and controllable reactivity, meanwhile maintain itsprotonated property.In this paper,6-azido-6-deoxychitosan was synthesized with regioselective substitution.Research results revealed the methods to control azido-substitution degree and property of6-azido-6-deoxychitosan. Condition to fabricated ionic gelation microspheres of6-azido-6-deoxychitosan was studied, as well as the structure and property of microspheres.The amino groups of chitosan were protected to generate N-phthaloyl-chitosan, and thenC6-OH was chemoselective bromination by NBS, short for N-bromosuccinimide, to prepare6-bromodeoxy chitosan. Bromine of6-bromodeoxy chitosan was substituted with azido group,and hydrazine hydrate made C2-NH2deprotected to synthesize6-azido-6-deoxychitosan.Azido-substitution degree of6-azido-6-deoxychitosan in this paper was up to0.6. Theaddition of a small amount of water can help to suppress the6-phthaloylation and controlC6-OH that can react in brominating and azidation. Degree of C6brominating was affectedby reaction temperature and raw ratio of pyranose and NBS. Degree of C6brominatingincreases with temperature and NBS raw ratio rise, and brominating reaction extent can reach0.9under the right conditions.6-bromodeoxy chitosan reacting with10times excess sodiumazide at80℃for4h gave extent of reaction up to0.9. As the presence of azido,6-azido-6-deoxychitosan showed decline in thermal stability and sensitivity to UV-light of365nm. At the concentration of1.3mg/mL,6-azido-6-deoxychitosan showed no toxicity toHMEC1cell, and gave prospect in biomedical material. Comparing reaction extent ofbrominating and azidation under different conditions, it makes sense that azido replacementcan be controlled by the number of C6-OH left in amino protection, and by controlling thedegree of brominating substitution under different NBS reactant ratio and temperature. 6-azido-6-deoxychitosan microspheres were fabricated in ionic gelation methods withsodium tripolyphosphate as gelling agent, and ionic gelation could be prepared only in the pHrange lower than3, azido-chitosan/sodium tripolyphosphate reactant ratio greater than5. Thediameter of ionic gelation particles was about134nm, and bovine serum albumin (BSA)encapsulation efficiency rated to77%. In release media of pH6.86,60%of entrapped BSA inazido-chitosan ionic gelation particles was released in2h abruptly and almost100%wasreleased in24h. In release media of pH1.5, ionic gelation particles of azido-chitosan released40%of entrapped BSA in8h and accumulative release was80%in72h. In general,azido-chitosan ionic gelation particles meet the basic requirement of the bowel release carrier.