Synthesis Of Chitosan Derivatives And Application In Liposome

Liposomes are mainly composed of lipid bilayer membrane distributed in water solution.As a formulation of targeting drug delivery systems(TDDS),liposomes have many advantages over common formulation,such as targeting ability,biodegrade ability with retarded drug release property and without toxibility.As drug carrier,liposomes can effectively improve the targeting ability,control the drug release rate,ensure stability of the drug involved and reduce side effects.After oral administration or injection administration of liposomes,the fast elimination rates have limited its clinical application.How to prolong the circulation time of liposomes in body had been payed extensive attentions from many research groups.In this paper,chitosan derivatives have been synthesized and used as liposome coating material with aim to enhance the circulation time and stability of liposome.The major contents and conclusions are as follows:Firstly,carboxymethyl chitosan was synthesised.To begin with,carboxymethyl chitosan was prepared by chitosan reacting with chloroacetic acid in concentrated alkaline.The reaction process was optimized by the L9(34)orthogonal experiment.Second,amphiphilic polymer was synthesized by conjuncting the lipoic acid to the CMCS,which could be used as nevol drug carrier.Its physical and chemical properties were also investigated.Secondly,Tegafuir liposome was prepared by method of rotary evaporation.Optimal formulation of tegafur liposome was obtained by studies of both single factor experiment and orthogonal experiment.The encapsulation efficiency of liposome after optimization can reach 67.09%.The morphology,size distribution and zeta potential of lipsome were measured by transmission electron microscope,particle size analyzer and zeta potential detector repectively.Thirdly,CMCS was applied in liposomes coating as a polvers materials.In vitro release properties of the coating liposome was investigated in phosphate buffer solution(pH=7.4).Results demonstrated that ordinary tegafur liposome soulution release rate about 95%in 3 hours,while liposome coated release 78%in 12 hours.This indicated that coated liposome could exhibit sustained-release properties.Lastly,the interaction of tegafur and bovine serum albumin has been studied by fluorescence spectroscopy and ultra-violet spectrum.The results showed that the quenehing mechanism of tegafur with BSA was mainly static quenched,the hydrophobic force played a major role in the interaction.The resulted showed molecule ratio of tegafur and BSA were arranged at approximate 1:1.This interaction probably altered the micro-environment of the tryptophan residues of BSA,eventually led to slight red shift of fluorescence emission wavelength of the tryptophan residues.