Abstract
The potential applications of cellulose nanomaterials in advanced composites and biomedicine makes it imperative to understand their pulmonary exposure to human health. Here, we report the results on the biodurability of three cellulose nanocrystal (CNC), two cellulose nanofibril (CNF) and a benchmark cellulose microcrystal (CMC) when exposed to artificial lung airway lining fluid (SUF, pH 7.3) for up to 7 days and alveolar macrophage phagolysosomal fluid (PSF, pH 4.5) for up to 9 months. X-ray diffraction analysis was used to monitor biodurability and thermogravimetry, surface area, hydrodynamic diameter, zeta potential and free radical generation capacity of the samples were determined (in vitro cell-free and RAW 264.7 cell line models). The CMC showed no measurable changes in crystallinity (xCR) or crystallite size D in either SUF or PSF. For one CNC, a slight decrease in xCR and D in SUF was observed. In acidic PSF, a slight increase in xCR with exposure time was observed, possibly due to dissolution of the amorphous component. In a cell-free reaction with H2O2, radicals were observed; the CNCs and a CNF generated significantly more •OH radicals than the CMC (p < 0.05). The •OH radical production correlates with particle decomposition temperature and is explained by the higher surface area to volume ratio of the CNCs. Based on their biodurability, mechanical clearance would be the primary mechanism for lung clearance of cellulose materials. The production of •OH radicals indicates the need for additional studies to characterize the potential inhalation hazards of cellulose.
Acknowledgements
The authors wish to thank the two companies that donated CNCs and Drs R. Sabo and A. Rudie at the US Department of Agriculture Forest Products Laboratory who donated some of the cellulose nanomaterials used in these studies. The authors also thank Drs M. Keane and R. Wells of NIOSH for critical review of this article. The research at NIOSH/CDC was funded by the US National Toxicology Program under Inter-Agency Agreement #11-NS11-04-M01. The research at West Virginia University was supported under contracts #212-2011-M-40726 and #212-2012-M-52337 from NIOSH/CDC. A.B.S. acknowledges the experimental assistance of M. G. Duling and R. B. Lawrence in carrying out the biodurability studies and associated measurements. M.S.S. acknowledges the experimental assistance of S. K. Pyapalli and U. Geddam in carrying out the X-ray diffraction and TGA measurements reported in this work.