Silica-coated nanoparticles with a core of zinc, L-arginine and a peptide designed for oral delivery.

Nanoparticle constructs for oral peptide delivery at a minimum must protect and present the peptide at the small intestinal epithelium in order to achieve oral bioavailability. In a reproducible, scalable, surfactant-free process, a core was formed with insulin in ratios with two established excipients and stabilisers, zinc chloride and L-arginine. Crosslinking was achieved with silica, which formed an outer shell. The process was reproducible across several batches and physicochemical characterisation of a single batch was confirmed in two independent laboratories. The nanoparticles (SiNP) entrapped insulin with high entrapment efficiency, preserved its structure, and released it at a pH value present in the small intestine. The SiNP delivered insulin to the circulation and reduced plasma glucose in a rat jejunal instillation model. The delivery mechanism required residual L-arginine in the particle to act as a permeation enhancer for SiNP-released insulin in the jejunum. The synthetic process was varied in terms of ratios of zinc chloride and L-arginine in the core to entrap the glucagon-like Peptide 1 analogue, exenatide, and bovine serum albumen. SiNP-delivered exenatide was also bioactive in mice to some extent following oral gavage. The process is the basis of a platform for oral peptide and protein delivery.