Study On Preparation And Properties Of Drug-loaded Galactosylated Chitosan Nanoparticles

Hepatopathy was a major class of serious disease that threating the health of the people. It included viral hepatitis, hepatic fibrosis, fatty livers, spirituous livers, medicinal hepatic lesion, hepatic cirrhosis, hepatoma and so on. Among them, chronic HBV hepatitis was very popular in China, as far as we know, about 1.3% of the Chinese people were suffered from this disease and thus caused a serious social problem.In traditional drug delivery mode, drugs were difficult to be transported to targeting site specifically and accurately, which caused a low bioavailability, toxicity and side effect on other normal organ. Galactosyl recognizes asialoglycoprotein receptor(ASGP-R) on liver cell surface specifically, and was widely used as ligands in designing liver-target drug delivery systems. Chitosan was widely used as drug carrier due to its good biocompatibility, biodegradation property, and non-toxcity. Nanodrug carrier system had became hotspot in the field of drug delivery system. Nanocarrier had greater stability, drug capacity, and better biomembrane permeability, thus had great potential in mordern drug delivery field. The work mainly studied the preparation of galactosylated chitosan nanoparitcles, and its application as delivery system for targeting delivery macromolecule drug to liver.Galactosylated chitosan was prepared by modifying chitosan with lactobionic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) and N,N,N',N'-tetramethylethylenediamine (TEMED) as catalyst. Galactosylated chitosans with different substitution degree of amino group were gained by controlling reaction time, and the substitution degree of amino group was measured by double sudden change potential titration method. IR spectrum of galactosylated chitosan indicated the existence of galactosyl in the products, and the IR spectrum result of galactosylated chitosan with different substitution degree of amino group was consistent with the result measured by double sudden change potential titration method.Galactosylated chitosan nanoparticle was prepared by the cross-linking of sodium tripolyphosphate and galactosylated chitosan. We discussed the effects of dispersing method, concentration of cross-linking agent and pH value of solution on the properties of nanoparticle. It was found that the nanoparticle was only formed under certain concentration range of galactosylated chitosan and sodium tripolyphosphate and pH value with homogeneous particle diameter and good dispersal. The result of dynamic light scattering and scanning electron microscope showed that the prepared nanoparticle had homogeneous particle diameter and good dispersal.Finally we discussed the encapsulation and releasing property of BSA-loaded nanoparticle. The effect of substitution degree of amino group, BSA concentration and particle diameter on encapsulation efficiency were studied. We found that the effect of substitution degree of amino group on encapsulation efficiency was not obvious, while higher BSA concentration and larger particle size lead to a greater encapsulation efficiency. The effect of substitution degree of amino group and particle diameter on releasing property was studied as well. It was found that substitution degree of amino group had little effect on releasing behavior and particle diameter had effects on releasing property, i.e., nanoparticles with larger diameter had more initial burst releasing with a higher velocity, while nanoparticles with smaller diameter had the reverse effect.