Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of intravenous drugs

Add time:08/26/2019    Source:sciencedirect.com

An amphiphilic chitosan derivate, N-octyl-O-sulfate chitosan (NOSC) was prepared by octylation of amino group at C-2 position and sulfonylation at C-6 position. Micelle formed by NOSC has great capability in solubilization of water-insoluble drug paclitaxel. Enormous attention was attracted by the potential application of NOSC as a new drug delivery system. Tritium labeled NOSC (3H NOSC) was injected by tail vein at dose of 13.44 mg/kg in mice; kidney retained the maximum amount of NOSC all the time even after 24 h following the injection. Pharmacokinetic parameters (the area under the plasma concentration–time curve, maximum plasma concentration, apparent plasma half-life of distribution phase and elimination phase, mean residence time, apparent volume of distribution, total body clearance) were obtained by fluorometric method in rats. The results showed a linear pharmacokinetics proceeding of FITC-NOSC in vivo. 75.4 ± 11.6% 3H NOSC of dose was excreted in urine over a 7-day period, urinary excretion was the predominant way of excretion of NOSC compared with bilary or fecal pathway. A series of safety studies consisted of acute toxicity study, intravenous stimulation study, injection anaphylaxis study, hemolysis study and cell viability assay were performed to warrant the biocompatibility of the NOSC as intravenous materials. The LD50 value of NOSC administrated by i.v. and i.p. were calculated as 102.59 and 130.53 mg/kg, respectively. No intravenous stimulation, injection anaphylaxis, hemolysis and cytotoxicity were observed in the safety studies. The tissue distribution, pharmacokinetics, excretion and safety study were persuasive for the potential application of NOSC as a new drug carrier.

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