| In order to prepare oxaliplatin (OXA) containing polymeric micelles with liver targeting ligand and to study its properties in vivo and in vitro, so as to realize the liver targeting drug delivery. The CS-SA (Chitosan-Stearic acid) and GA-CS-SA(Glycyrrhetinic acid-Chitosan-Stearic acid) were all synthesized by amide reaction between the amino-groups of CS and the carboxyl groups of SA or GA in the presence of1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuc-cinimide (NHS). The chemical structures of CS-SA and GA-CS-SA were confirmed by’H NMR analysis. The substitute degree (SD) of amino groups of CS-SA or GA-CS-SA was measured by TNBS method. CS-SA micelles and GA-CS-SA micelles were prepared by probe supersonic method. Pyrene, as a fluorescence probe, was used to determine critical micelle concentration (CMC). Steady-state fluorescence-quenching method was used to estimate the hydrophobic micro-domain (AN) per CSO-SA or GA-CS-SA molecule. The average diameter and zeta potential of micelles were detected by dynamic light scattering. The spherical morphology of CS-SA and GA-CS-SA micelles were detected by transmission electron microscopy (TEM). It was clear from the’H-NMR spectrum that SA and GA were coupled to CS successfully. The SD of SA and GA were16.2%and5.6%. The CMC of GA-CS-SA was17.94±0.48μg/ml. The AN of GA-CS-SA was2.09. The GA-CS-SA micelles have a unimodal size distribution and a small size. The CS-SA and GA-CS-SA micelles are regular spherical particles, their surfaces are smooth and no conglutination. The OXA-CS-SA and OXA-GA-CS-SA micelles were prepared successfully. The encapsulation rates were66.93%and71.7%; the release of OXA in vitro were slow. In vivo tissue distribution results of OXA showed that the OXA-GA-CS-SA micelles relatively increased the distribution of OXA in the liver of mouse, which achieved a certain degree of targeting. All the results suggest that GA-CS-SA is a potential liver targeting drug carrier. |
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