Developing a Solution for Nasal and Olfactory Transport of Nanomaterials

Nanotechnology is one of the most rapidly developing areas of the economy and involves the study and control of matter in the nanoscale. The nanoscale is the size range from 1 to 100 nm. Recently, some nanomaterials have demonstrated the ability to enter the brain through the olfactory pathway from the nose to the brain. ⁠This pathway can potentially enable inhaled nanomaterials to enter the brain. Inhalation exposures are technically difficult and expensive. Intranasal instillation is a potential screening tool for evaluating nose to brain transport. However, particles in aqueous media tend to agglomerate and agglomerated particles often act like larger particles in terms of surface area, toxicity, and size thresholds for transport pathways. For neuronal transport within the brain, the upper size limit is estimated to be approximately 100 nm. Therefore, nanomaterials must be adequately dispersed in the vehicle used for instillation in order to evaluate their potential for transport from the nose to the brain.

Because 100 nm is the upper size limit estimated for transport within the central nervous system, components of dispersion media may need to be different from dispersion media used to evaluate toxicity in other tissues. For example, albumin, a protein which is useful in dispersion media developed for the lung, can interact with nanomaterials and increase their size. In addition, neurons transport sodium out of the cell, suggesting that a dispersion medium to evaluate nose-to-brain transport should avoid high sodium concentrations. To overcome issues with the size of albumin and other proteins as well as the potential effects of sodium and phosphate, we hypothesized that free amino acids, a balanced electrolyte solution, and a mixture of phospholipids could produce a solution that both dispersed nanomaterials and was compatible with neuronal transport. This study describes and characterizes a solution for nasal and olfactory transport (SNOT) that can disperse nanomaterials and dyes with nanoscale dimensions, enabling intranasal instillation so that potential nose-to-brain transport can be evaluated.