Novel Solid Lipid Nanoparticle with Endosomal Escape Function for Oral Delivery of Insulin

ACS Applied Materials & Interfaces
Yining XuYuan Huang

Abstract

Although nanoparticles (NPs) have been demonstrated as promising tools for improving oral absorption of biotherapeutics, most of them still have very limited oral bioavailability. Lyso-endosomal degradation in epithelial cells is one of the important but often-neglected physiological barriers, limiting the transport of cargoes across the intestinal epithelium. We herein reported a solid lipid nanoparticle (SLN) platform with a unique feature of endosomal escape for oral protein drug delivery. The SLNs consisted of a solid-lipid shell, which contained an endosomal escape agent (GLFEAIEGFIENGWEGMIDGWYG, HA2), and an aqueous core that is loaded with insulin (INS HA2-O-SLNs). SLNs without and with the HA2 peptide in the aqueous core (INS SLNs and INS HA2-W-SLNs, respectively) were used as the control groups. Our study showed that INS HA2-O-SLNs effectively facilitated the escape of the loaded insulin from the acidic endosomes, which preserved the biological activity of insulin to a greater extent during the intracellular transport. The spatial location of the HA2 peptide was demonstrated to determine the endosomal escape efficiency. As demonstrated in the intracellular trafficking of SLNs, INS HA2-O-SLNs displayed much less distrib...Continue Reading

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