| Liposomes have a biological structure similar to bilayer membrane.As drug carriers,they have ability of targeting,delayed release,reducing the dose and drug toxicity.But the targeting of unmodified liposomes focus on organs that are rich in reticuloendothelial cell,while in other parts of organs their targeting are not obvious during the therapy.Meanwhile,traditional liposomes are not stable in vivo and in vitro, easily oxidized and hydrolyzed,and their bilayer membrane will also easily convert the phase,aggregation and fusion will happen between liposomes,then the drug encapsulated in liposomes will easily seepage from it,and so on.In recent years,in order to improve the targeting and stabiliy in vivo and in vitro of liposomes,many scholars have prepared the liposome membrane of surface modification,which is adding certain auxiliary agents in the composition of membrane material,such as cholesterol,soy sterol,polyvinyl alcohol and polyethylene glycol to increase the stability of lipid bilayer membrane and enhance the stability of liposomes in vitro and in vivo.The study of this dissertation is mainly to use biodegradable,non-toxic,water-soluble,low-molecular-weight and good biocompatibie chitosan derivatives on liposomes surface-modifying,for building a high stability and special targeting liposomal drug delivery systems.Main contents and conclusions are as follows:Firstly,chitosan as raw materials,hydrosoluble carboxymethyl chitosan was synthesized through the etherealization reaction under basic condition between chitosan and chloroacetic acid.Then,with existence of sodium borohydride,reductive amination reaction happened between carboxymethy chitosan and lactose,and galactose carboxymethyl chitosan was obtained.We took the method of infrared spectrum to characterized the structure of synthetic products,at the same time we measured the degree of substitution of carboxymethyl and galactose group on amino-group by the method of two abrupt change conductometric titration.The result indicated that the reaction of carboxymethyl mainly happened on the group of hydroxyl of C6,and the degree of substitution was about 0.65.While the reaction of galactose happened on amino group of C2,the degree of substitution was 0.20 or so.Secondly,we prepared the liposomes by the film-ultrasonic wave dissolving techniques.Taking entrapment efficiency as an index,the preparing prescription of liposomes were screened and the process of liposomes were optimized through the orthogonal experiment,using scanning electron microscopy and Zeta potential of ultra-fine-grained and detector for characterization of liposomes.The experimental results showed as followed.The best prescription was that mass ratio of phospholipids /glycyrrhizic acid was 10:1,and the concentration of carboxymethyl chitosan (galactosyl-carboxymethyl chitosan) was 0.3%.When the substitution degree of carboxymethyl was 0.65 and the substitution degree of galactosyl was 0.22,the mean diameter of liposomes modified by carboxymethyl was 122nm,and the zeta electric potential was -53.2mV.While the mean diameter of liposoems that modified by galactosyl was 112nm,and Zeta electric potential was -50.7mV,the morphology of liposomes was more structured and uniform,with smaller particle size distribution,at the same time had a high drug entrapment efficiency,about 80%.Finally,the dissertation studied liposomal release properties in vitro,investigated different concentrations of material,substitutional degrees and releasing mediuns at different pH values,which had effect on the performance of liposomal releasing properties.Through the experimental study of release in vitro,it was found that glycyrrhizin liposomes modified by both carboxymethyl chitosan and galactosyl-carboxymethyl chitosan showed slow-release and controlled release performance.At preliminary stage of an hour,drug releasing accumulated to 15%on average,then it slowly released drug,in twelve hours drug releasing accumulated to 45%or so.It is showed that the liposomes can build a potential initiative liver-targeted liposome drug release delivery system.And glycyrrhizin liposomes modified by carboxymethyl chitosan have good pH sensitivity of the intellective controlled release characteristics in vitro.
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