C-DMSA Loaded VES-g-CSO/VES-g-CS Micelle Delivery System For The Treatment Of Mercury Poisoning Rats

Based on the superior properties of chitooligosaccharides(CSO),chitosan(CS)and vitamin E succinate(VES),vitamin E succinate grafted chitooligosaccharides(VES-g-CSO)、vitamin E succinate grafted succinate grafted chitosan(VES-g-CS).Theranostic Hg2+fluorescent probe C-DMSA was successfully synthesized from coumarin aldehyde compounds(abbreviated coumarin aldehyde)and dimercaptosuccinic acid(DMSA).VES-g-CSO and VESg-CS were utilized in the preparation of C-DMSA loaded micelles(C-DMSA@VES-g-CSO/VES-g-CS micelle).The physiochemical properties as well as treat effects of C-DMSA@VES-g-CSO/VES-g-CS micelles delivery system were further investigated.VES-g-CSO and VES-g-CS were synthesized and characterized by 1H-NMR and FI-IR.Degree of substitution(DS)of VES-g-CSO and VES-g-CS were determined by elemental analysis(DSVES=1.24%,2.97%).The critical micelle concentrations(CMCs)of VES-g-CSO,VES-g-CS were tested through the pyrene fluorescence probe method.The CMCs of them were 61.46 μg/mL,17.62 μg/mL,respectively.C-DMSA@VES-g-CSO/VES-g-CS micelles were prepared by solvent evaporation method.C-DMSA@VES-g-CSO/VES-g-CS micelles with particle size of 145.2 nm,Zeta potential of 24.1 mV and loading effiency of 6.9%were prepared and used for further application.The transmission electron microscopy(TEM)images showed that the C-DMSA@VES-g-CSO/VES-g-CS micelles were spherical and distributed uniformly.The in vitro release experiment of PBS with pH 7.4 showed that C-DMSA@VES-g-CSO/VES-g-CS micelles had a burst release of 15.4%in 1 h,the drug cumulative release of C-DMSA@VES-g-CSO/VESg-CS micelles were 60.7%in 72 h.L929 mouse fibroblast cells were used to study the cytotoxicity and cell uptake experiments.The MTT results showed that no significant cytotoxicity was found for the CDMSA@VES-g-CSO/VES-g-CS micelle on L929 cells.Cellular uptake experiments showed that C-DMSA@VES-g-CSO/VES-g-CS micelles can be taken up by L929 cells.MTT results showed that C-DMSA loaded micelles can decrease the toxicity of Hg2+to the L929 cell and increase cell viability.Mercury poisoning rats were established by intraperitoneal injection of HgCl2.After injected via the tail vein with different doses of C-DMSA@VES-g-CSO/VES-g-CS micelle(15 mg/kg,30 mg/kg),the liver coefficient,serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)activity,and contents of hepatic mercury and blood mercury were examined.Compared to the mercury poisoning rats,C-DMSA@VES-g-CSO/VES-g-CS micelle significantly reduced the liver coefficient and activity of AST,ALT.Besides,CDMSA@VES-g-CSO/VES-g-CS micelles could effectively reduce hepatic mercury and blood mercury levels.All the results indicated that C-DMSA@VES-g-CSO/VES-g-CS micelles had a certain therapeutic effect on mercury poisoning rats.