Smart Protein-Based Formulation of Dendritic Mesoporous Silica Nanoparticles: Toward Oral Delivery of Insulin

Abstract

Oral insulin administration still represents a paramount quest that almost a century of continuous research attempts did not suffice to fulfill. Before pre-clinical development, oral insulin products have first to be optimized in terms of encapsulation efficiency, protection against proteolysis, and intestinal permeation ability. With the use of dendritic mesoporous silica nanoparticles (DMSNs) as an insulin host and together with a protein-based excipient, succinylated β-lactoglobulin (BL), pH-responsive tablets permitted the shielding of insulin from early release/degradation in the stomach and mediated insulin permeation across the intestinal cellular membrane. Following an original in vitro cellular assay based on insulin starvation, direct cellular fluorescent visualization has evidenced how DMSNs could ensure the intestinal cellular transport of insulin.

Keywords: beta-lactoglobulin tablets; cellular insulin starvation; dendritic mesoporous silica nanoparticles; oral insulin dosage; transcellular epithelial transport.