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In Vivo Toxicity Profile of NN-32 and Nanogold Conjugated GNP-NN-32 from Indian Spectacled Cobra Venom
Saurabh S Attarde1, Sangeeta V Pandit1
1Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India.
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.
Insights
Gold nanoparticle conjugation of NN-32 toxin significantly reduced its in vivo toxicity in mice. This nanotechnology approach enhances the safety profile of NN-32, a promising anti-cancer agent derived from Naja naja venom.
Area of Science:
- Biochemistry
- Nanotechnology
- Pharmacology
Background:
- NN-32 toxin from Naja naja venom exhibits cytotoxicity against cancer cell lines.
- High toxicity of NN-32 hinders its drug development potential.
- Conjugation with gold nanoparticles (GNP-NN-32) aimed to mitigate NN-32 toxicity while preserving efficacy, showing promise in in vitro studies.
Purpose of the Study:
- To evaluate the in vivo toxicity profile of NN-32 and its gold nanoparticle conjugate, GNP-NN-32.
- To compare the safety and toxicity of the native toxin versus the nanoparticle-conjugated form in a living organism.
Main Methods:
- In vivo acute toxicity study to determine the LD50 dose of GNP-NN-32.
- In vivo 30-day sub-chronic toxicity assessment.
- Hematological and serum biochemical analyses.
- Histopathological examination of various mouse tissues.
- In vitro cellular and tissue toxicity assays.
Main Results:
- The LD50 dose of GNP-NN-32 was determined to be 2.58 mg/kg (intraperitoneal) in Swiss male albino mice.
- Sub-chronic toxicity studies revealed significantly reduced toxicity for GNP-NN-32 compared to NN-32 alone.
- In vitro studies indicated that NN-32 alone significantly inhibited human lymphocyte and mouse peritoneal macrophage cells.
Conclusions:
- Gold nanoparticle conjugation effectively reduces the in vivo toxicity of NN-32 toxin.
- GNP-NN-32 presents a safer alternative to pure NN-32 for potential therapeutic applications.
- Nanoparticle-based drug delivery systems can enhance the therapeutic index of cytotoxic agents.
