Synthesis And Photo-responsive Behaviors Of Carboxymethyl Chitosan-based Hollow Nanospheres

The stimuli-responsive polymer compound refers to the substances that theirown physical or chemical properties changes are sensitive to external stimulusresponses under certain conditions, such as temperature, pH and other stimuluses.Compared to traditional external stimulus, light stimulation has its unique advantages,because additional time, position and angle of light can be precisely controlled, acontrolled release form by this stimulation can be achieved. In this paper, we usesuccinic anhydride as the connecting arm grafted the light-responsive2-nitrobenzylalcohol with amino group on carboxymethyl chitosan. After that we use the producedlight-responsive carboxymethyl chitosan derivatives as the raw material to get thelight-responsive hollow nanocapsules. The main research works and conclusions areas follows:I. Light-responsive carboxymethyl chitosan derivatives were prepared, itsstructure was determined, and its related properties were studied.Using the intermediate products which obtained from the reaction betweenring-opening succinic anhydride and nitrobenzyl alcohol reacted with carboxymethylchitosan to get the amphiphilic carboxymethyl chitosan derivatives linked by amidebond which integrate from intermediates’s carboxyl group and carboxymethylchitosan’s amino group. Structure of derivatives was detected by IR and1HNMRmethods. Light response of the intermediate and carboxymethyl chitosan derivativeswas determined and researched by TLC, UV, HPLC and other inspection techniquesrespectively.II. The stability, light response and pH sensitivity of the hollow nanocapsulesprepared from carboxymethyl chitosan derivatives was studied.(1) The carboxymethyl chitosan derivatives were evenly dispersed into thesystem, by adjusting the pH and ultrasonic treatment, hollow nanocapsules wereprepared, and then glutaraldehyde (GA) was used as the auxiliary cross-linking agent,the hollow nanocapsules with good stability were finally obtained. The transmissionelectron microscopy (TEM) shows, both light-responsive hollow nanocapsules andGA-crosslinked hollow nanocapsules have obvious hollow structure, neatmorphology, equal distribution, and uniform particle size. Compared with hollow nanocapsules before cross-linking, the hollow nanocapsules after GA-cross-linkinghave a tighter shell structure.(2) The dynamic light scattering (DLS) results reveal that, the hollownanocapsules after GA-cross-linking present better stability, smaller average diameter,and more uniform distribution.(3) Both hollow nanocapsules before and after GA-cross-linking show excellentlight response. The light-responsive groups of the GA-cross-linked nanocapsules arecleaved under light stimulate, the cross-linked networks of the shell are destroyed, theparticle size becomes bigger, and the distribution gets wider; In contrast, thelight-responsive groups of the hollow nanocapsules before cross-linking are alsocleaved under light stimulus, which changes the ratio of hydrophilic groups andhydrophobic group and weaken the hydrophobic interaction, and the hollownanocapsules crack eventually.(4) The GA-cross-linked hollow nanocapsules present obvious pH sensitivity.When pH value falls in the lower region, the smaller diameter is obtained, and in thehigher region, the bigger. But when pH value is beyond a certain region, the diametertends to be smaller. The light-responsive groups content of the hollow nanocapsuleshave a little influence on the pH sensitivity, duing to the same dosage of auxiliarycross-linking agent glutaraldehyde. The hollow nanocapsules precipitate out when pHlower than3.0, but can again disperse in solutions with appropriate pH value.III. The drug release of bentazone-loaded nanocapsules was investigated, itprovides a theoretical basis of the nano-model development in the field of nano drugcarrier.(1) Drug-loaded hollow nanocapsules were achieved though regarding hollownanocapsules as carrier, bentazone as drug model, using method of situ package load.The amount of drug used influences drug loading content and drug loading efficacyof hollow nanocapsules: with the increase of the amount of drug used, drug loadingcontent also increases; but when the increase of the amount of drug used, drugloading efficacy first increases but then decreases, reaching the maximum at a criticalpoint.(2) Drug in nanocapsules releases under light stimulus: under the condition oflight stimulus, the release of drug is fast, while under the condition of no light stimulus, the release of drug is very slow even no release. The form of nanocapsulesinfluences its drug release: in dark environment, the release trend of three kinds ofnanocapsules is the same, having no or very little drug release; under the condition oflight stimulus, the lower the degree of light-responsive groups in drug-loadednanocapsules, the faster the rate of drug release.