Study On Preparation Of Isinglass Primordia Composite Sponge And Used As Sustained-release Membrane

Tumor chemotherapy used for some solid tumors has many drawbacks, including low selectivity, and great systemic side effects. The controlled-released membrane combined with nanotechnology can maintain effective drug concentration for a longer time, improve drug targeting and reduce systemic side effects. At present, the collagen using for the implantable controlled-released carrier is extracted mainly from terrestrial animals, such as pigs and cattles. But its application is limited for the occurrence of diseases like mad cow disease and mouth and foot disease, and the causes of religion and customs and so on. Fish scales, skin and other aquatic waste are rich in collagen without the previously discussed infectious diseases, and the collagen amino composition has no obvious difference from terrestrial mammals, therefore, it has the development and utilization value. However, the related research of collagen used as the implantable drug controlled-released carrier materials is rarely reported.In this paper, the collagen was isolated from sliver carp skin through enzymatic hydrolysis, and the collagen-chitosan composite sponges were fabricated by crosslinking with glutaraldehyde (GA) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The results indicated that the composite sponges had good biocompatibility and hemostatic effect, the best proportion of collagen and chitosan is 1:0.25 (w/w), and GA will be more suitable as a crosslinking agent than EDC.Biotin modified cholesterol conjugated glycol chitosan polymer (Bio-CHGC) was fabricated via three step reaction synthesis, using cholesterol, succinic anhydride, ethylene glycol chitosan and biotin as the raw materials. It was characterized by infrared spectroscopy, nuclear magnetic resonance (NMR), and element analysis. Adriamycin was chosen as a model drug, and the drug-loaded nanoparticles were prepared by utilizing an established probe ultrasound technique. Transmission electron microscope showed its’spherical morphology. With initial levels of the drug increased, the drug loading content of all nanopaticles increased, and the encapsulation efficiency decreased. The size of particles increased as the drug loading content increased. The release kinetics in PBS solutions with different pH indicated that the release rate decreased with the increase of drug loading content and the pH value. The stability results suggested that the nanoparticles were stable in physiological conditions.The collagen-based controlled-release membranes were fabricated with adriamycin-loaded Bio-CHGC nanoparticles, abandoned silver carp collagen, and chitosan. The swelling, degradation and release test in vitro and cytotoxicity assay of membrane were examined. The results revealed that the drug release rate of controlled-released membrane is slower than drug-loading nanoparticles under the same conditions. The controlled-release is mainly through the degradation of matrix, and diffusion is an auxiliary form. In addition, the Bio-CHGC membrane has higher cell inhibition rate than CHGC membrane (without biotin). The above results revealed that the membrane had dual sustained release and targeting effects, indicating it could be developed as a new type of antitumor agents.