In Vivo Toxicity Profile of NN-32 and Nanogold Conjugated GNP-NN-32 from Indian Spectacled Cobra Venom

Abstract

Background: NN-32 toxin, which was obtained from Naja naja venom and showed cytotoxicity on cancer cell lines. As the toxicity of NN-32 is the main hurdle in the process of drug development; hence, we have conjugated NN-32 toxin with gold nanoparticles (GNP-NN-32) in order to decrease the toxicity of NN-32 without reducing its efficacy, GNP-NN-32 alleviated the toxicity of NN-32 in in vitro studies during the course of earlier studies. In continuation, we are evaluating in vivo toxicity profile of NN-32 and GNP-NN-32 in the present study.

Objective: To study in vivo toxicity profile of NN-32 and nanogold conjugated GNP-NN-32 from Naja naja venom.

Materials and methods: We have carried out in vivo acute toxicity study to determine LD50 dose of GNP-NN-32, in vivo sub-chronic toxicity for 30 days, haematology, serum biochemical parameters and histopathology study on various mice tissues and in vitro cellular and tissue toxicity studies.

Results: The LD50 dose of GNP-NN-32 was found to be 2.58 mg/kg (i.p.) in Swiss male albino mice. In vivo sub-chronic toxicity showed significantly reduced toxicity of GNP-NN-32 as compared to NN-32 alone.

Discussion: In vitro cellular toxicity studies on human lymphocyte and mouse peritoneal macrophage showed significant inhibition of cells by NN-32 alone.

Conclusion: Conjugated GNP-NN-32 toxin showed less in vivo toxicity as compared to pure NN-32.

Keywords: GNP-NN-32; Gold nanoparticles; LD50; Naja naja; histopathology; serum biochemical parameters; sub-chronic toxicity.