Investigation of chitosan, its depolymerized products, and nanoformulation as novel anticonvulsants

Abstract

Objectives Chitosan is a natural biopolymer that possesses various biological activities. The aim of the current study was to evaluate the potentiality of chitosan and its enzymatically depolymerized products as anticonvulsants. Materials and methods In the current study, chitosan enzymatic depolymerization was carried out using Bacillus cereus chitosanase followed by fractionation of the produced chitooligosaccharides. Phase I anticonvulsant activity of chitosan as well as its enzymatically depolymerized products was evaluated using pentylenetetrazole-induced seizures, maximal electric shock, and neurotoxicity tests. In phase II, median effective dose, median toxic dose, and protective index were determined. In addition, γ-aminobutyric acid brain level and acute toxicity were evaluated. Results and conclusion The results indicated that the fraction with the lower degree of acetylation and longer chains of glucosamine (COSH) possessed rapid onset of action with the highest protection (75%) at 0.5 h and long-acting effect for 4 h. In addition, the median effective dose of COSH was 12.7-fold more potent than the reference ethosuximide, whereas in the maximal electric shock test, COSH showed lower potency than phenytoin. The median toxic dose was 1.4-fold and 7.9-fold higher than ethosuximide and phenytoin, respectively. The protective index was 18.1-fold and 3.98-fold higher than ethosuximide and phenytoin, respectively, with a significant increase in γ-aminobutyric acid neurotransmitter brain level. In an attempt to prolong the anticonvulsant effect of COSH, a nano-formulation was carried out in which the particle size was estimated as 188.7±0.26 nm. After that, an equivalent dose of a combined treatment of COSH and the nanoformula (each 15 mg/kg) was evaluated in which a prolonged effect was achieved up to 24 h.