Synthesize And Characterization Of Chitosan-based Derivatives And Their Evaluation In Vitro

Chitosan is valuablely developed and applied in medical fields such as tissue engineering scaffold,gene carrier,membrane dialysis,surgical trauma coating material and drug release material for its physiological activity,antibacterial property and blood compatibility.In this paper,many research results that chitosan and its medical-aimed derivatives are used in the field of tissue engineering and drug release are reviewed.The theoretical basis of improving blood compatibility of chitosan is discussed by analyzing its antibacterial property and blood compatibility.To seek the design idea of novel controlled release system for drugs,the shortage of controlled drug release system of chitosan is analyzed.The research aim of this paper is to prepare based-chitosan medical material with excellent property.The content are as follows:①using the chitosan with low molecular weight to synthesize its derivatives with different functional group modified;②research on chitosan/polyester/polyether composites;③design and initial study on chitosan/PHB copolymer;④preparation of two novel controlled drug release based-chitosan and their controlled release behavior;⑤comparison of antibacterial property and mechanism among based-chitosan materials;⑥design of improving chitosan's blood compatibility and determine the effect.So all the content are explained as follows:In chapter 2,chitosan samples with different molecular weight and different degree of deacetylation(DD)are prepared,and chitosan water-soluble derivatives such as O-carboxymethyl chitosan(O-CMCTS),N,O-carboxymethyl chitosan(N,O-CMCTS), maleoyl chitosan(M-CTS)and hydroxypropyl chitosan(HP-CT)are synthesized.The change of functional group of chitosan derivatives is determined by IR spectra,and molecular weight and the content of functional group are examined by viscosimetry and potentiometric analysis,respectively.The moisture-absorption and -retention and thickening property of derivatives are better than chitosan with DD= 100%.To compare the macromolecule composite with small molecular derivative,based on the blended of homogeneous phase,CTS/PHB graft copolymer is prepared.The structure of graft copolymer is validated by ~1H NMR and IR.Chitosan is blended with hydrophobic poly-hydroxybutyrate(PHB)and hydrophilic polyethylene glycol(PEG)under homogeneous phase to prepare CTS/PHB and CTS/PHB/PEG blend films with different mass ratio in chapter 3.The composites are characterized by IR,WAXD,DTA,SEM and ~1H NMR,and the results show there is a good compatibility of blend between chitosan and PHB,and PEG improves the effect of blending chitosan with PHB.The change of films with different mass ratio on swelling index and surface microtopography is not related to the chitosan's content of film,but is helpful to analyze the difference in biology property of blend films.In chapter 4,using E.coli and St.aureus as tapical test bacteria,the antibacterial activity of chitosan water-soluble derivatives and composites are estimated by colony counting method and inhibition zone method,respectively.The results show that the series of chitosan,derivatives and chitosan composites still have good antibacterial activities,and derivative modification method dosen't result in negative effect to the antibacterial activity of chitosan.The evaluation of blood compatibility including hemolysis,coagulation and platelet adhesion is carried out on chitosan chemical derivatives and composites in chapter 5. Results showes that introducing carboxyl group improves the anti-coagulation of chitosan,and except HP-CT,the hemolysis ratio of the other three derivatives are in accordance with national standard.CTS/PHB blend films have lower hemolysis ratio, longer plasma recalcification time,more smooth dynamic clotting time curve and less adsorbed platelets than chitosan,so they have a good anticoagulant activity.Adding PEG make the former changes more obvious.The CTS/PHB copolymer has excellent performance with its hemolysis ratio of 3.5%,plasma recalcification time of 200 s, smooth dynamic clotting time curve and no adsorbed platelets on the surface of film.In chapter 6,cross-linking adsorbed chitosan resin is synthesized by the template-occupying,and the chitosan resin is also prepared by the general methods. Then the three resins are used for adsorbing salicylic acid and the releasing behavior are estimated by contrast to each other.Results indicate that the resin particles are close to nano-scale and well distributed.It adsorption capacity is big(accumulative total up to 8.64 mmol/g),controlled releasing behavior is clear,and it can effectively restrain the burst effect and has a better ability in answer to pH.In chapter 7,polyelectrolyte complex drug controlled release particles—CTS/TPP/Aspirin(CPA)is prepared.The particle size distribution is between 5 and 300μm,and entrapment efficiency is up to 45.3%.To overcome the shortage of CPA (nonsteady when it meets with acid),CPA polyester micro cyst(CPAB)was prepared by solvent evaporation method.Compared with CPA,the entrapment efficiency of CPAB is a little lower,but the drug release behavior in vitro confirms CPAB can effectively settle the problem of CPA's instability under acidified condition and has a long release period.Meanwhile,polar agglomeration behavior on the surface of CPA particles is effectively improved because of covering hydrophobic polyester.The particle size distribution of CPAB is better than CPA,and the microcyst with particle size of 100 nm account for about 80%.