Toward a greener multifunctional pharmaceutical excipient: in vivo safety evaluation of nanofibrillated cellulose from tobacco stalk

Abstract

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175–5,000 mg·kg⁻¹) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg⁻¹ per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.

GRAPHICAL ABSTRACT

Keywords:

• Nanofibrillated cellulose
• acute toxicity
• subchronic toxicity
• tobacco stalk
• pharmaceutical excipient
• sustainability

Acknowledgments

The authors would like to thank the LAPETOX research group, especially MSc Juliana Fank Gomes, Dr Marina Tuerlinckx Costa Valle and, MSc Mateus Belmonte Macedo from Programa de Pós-Graduação in Neurosciences of UFRGS for their contributions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original dataset used to generate Tables and Figures in the manuscript are available.

Additional information

Funding

This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES), under grant Finance Code 001.