The Study On Modification Of Cellulose By ATRP In Ionic Liquid And Its Application In Controlled Drug Release

Cellulose has extensively used in biological and medical fields own to its advantage of excellent biocompatibility and biodegradability.The pH-sensitivity cellulose graft copolymers were obtained by introducing pH-sensitivity groups on the cellulose molecular structure.The pH-sensitivity cellulose polymeric micelle targeted delivery the drug which encapsulated in the micelles depending on the difference in pH of human tissue and it also can enhance bioavailability of drugs and reduce the side effects of drugs.So in this papper,the ionic liquids that had strong dissolving ability about cellulose were used as reaction medium.Combining with advantage of controlled/living polymerization processes about atom transfer radical polymerization(ATRP).The different pH-sensitivity molecules were evenly grafted on the cellulose chain backbone in order to realize the sustained-and controlled-release drug delivery of pH-responsive cellulose polymeric micelles in different pH of physiological environment.In this research,the poly 4-vinyl pyridine and poly(tert-butylmethacrylate)were evenly grafted on microcrystalline cellulose chain backbone respectively by ATRP in ionic liquid 1-allyl-3-methyl-imidazole chloride([AMIM]Cl).The pH-responsive weak alkaline polymer MCC-g-P4 VP and weak acid polymer MCC-g-PMAA were obtained by poly(tert-butylmethacrylate)hydrolysis into Poly(methacrylic acid).The optimal synthesis conditions of the two polymers were obtained.The molecular structure of two polymers was characterized by FT-IR and NMR.The result of GPC revealed that the side chain of two polymers had narrow molecular weight distribution and uniform molecular weight.The surface tension measurements results hinted that MCC-g-P4 VP and MCC-g-PMAA polymeric micelles had low critical micelle concentration(CMC)and apparented excellent stability.The polymeric micelles diameter,micellar morphology and pH-responsive performance of polymeric micelles were characterized by means of TEM 、 DLS and UV-Vis.The results show that the two polymers could self-assemble into spherical micelles.The hydrodynamic diameter of was less than 200 nm and the polymeric micelles had uniform particle size distribution.The diameter and transmittance of two polymeric micelles revealed corresponding transformation in different pH solution.The two polymeric micelles had shown excellent pH-responsive.The drug encapsulation property and controlled drugs release of MCC-g-P4 VP and MCC-g-PMAA polymeric micelles in different pH solution were investigated by usingsoluble rhodamine B(Rh B)and insoluble aspirin(ASP)as the model drug.The drug release mechanism of different solubility drugs released from two polymeric micelles in different pH solution was analyzed by using several kinetics models.The results show that MCC-g-P4 VP polymeric micelles had excellent drug encapsulation property for Rh B and ASP.The drug loaded micelles have a spherical morphology with core-shell structure.The cumulant release of drug in acidic environment is higher than that in basic environment.The drug release pattern was conformed to the first-order kinetics model in acidic environment.In basic and neutral conditions,the drug release from micelles was followed the Ritger-Pappas model.In basic environment,the cumulantive drug release of MCC-g-PMAA drug loaded micelles higher than that in acidic environment.The drug loaded micelle shows excellent properties of drug controlled-release.The fitting results of the drug release kinetics equation showed that the release mechanism of MCC-g-PMAA polymeric micelles for two drugs was dominated by diffusion and erosion in acidic and neutral environment.In basic environment,the two drugs release mechanism was dominated by diffusion.