[CRBS Seminar] Morphology controlled nanomaterials to navigate mucosal barriers

Abstract:Administering drugs to mucosal sites in the body can offer several advantages. However, the design of drug carriers that can prevent dilution with physiological fluids and clearance by mucus remains a significant challenge for the scientific community. In this context, nanomaterials (NMs) coated with mucoadhesive polymers have demonstrated their potential in addressing these issues, owing to their small size and adhesive properties. Nevertheless, while there has been extensive research on the size and surface properties of NMs, there is a noticeable lack of investigations into how the morphology of NMs influences their interactions with mucosal barriers.

Our envisioned strategy involves considering the morphology of NMs as a crucial parameter for preventing mucus dilution by biological fluids, facilitating their accumulation in high concentrations near the mucosal epithelium, and promoting their internalization by epithelial cells. To understand whether NM morphology impacts their transport within mucus and their mucoadhesive properties, robust technological tools are required to create NMs with controlled characteristics.

In this regard, our research group has developed complementary processes for designing NMs with controlled morphology, allowing us to regulate aspect ratio, size, and surface modifications simultaneously. We generated nonspherical particles, referred to as "nanoplatelets," through the supramolecular and hierarchical self-assembly of α-cyclodextrin and hydrophobically modified polysaccharides with palmitic acid in water. Atomic force microscopy characterization revealed that these nanoplatelets possess flat surfaces, sharp edges, and a high aspect ratio (approximately 20).

Our findings indicate that nanoplatelets exhibit enhanced mobility in biological fluids and increased cellular internalization compared to spherical particles. Furthermore, they demonstrate superior bioadhesive properties, and through real-time in vivo imaging using a rat model, we observed that nanoplatelets exhibit longer residence times in the intestine and bladder than spherical particles. Finally, we observed that nanoplatelets possess intrinsic anti-inflammatory and anti-infective activity, whereas spherical particles remained inactive.