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Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin

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Abstract

Although nanoparticles (NPs) have emerged as a promising strategy to improve oral absorption of insulin, most of them still have minimal oral bioavailability due to the harsh gastrointestinal (GI) environment and epithelial barriers. A novel platform of oral insulin delivery is herein proposed based on amphiphilic cholesterol-phosphate conjugate (CHP). The CHP was synthesized with a cholesterol moiety as a hydrophobic block and a phosphate group as a hydrophilic block. The structural characteristics of CHP made cholesteryl moieties to point outward to form a shell coated on the surface of NPs, and phosphate groups toward inside as the core via the water-in-oil (W/O) emulsion method. The additional Ca2+ could chelate to phosphate groups in the core to bind adjacent phosphate groups and further increased the stability of NPs (CP-Ca NPs). Phospholipid and glycocholate were modified on the surface of CP-Ca NPs to form hydrophilic corona coated CP-Ca NPs (Hc@CP-Ca NPs) and didn't change the structure of CP-Ca NPs. The NPs exhibited high encapsulation efficiency (>95%) and had high stability in the GI tract by reducing insulin release and protecting insulin from enzymatic degradation. Compared to free insulin, Hc@CP-Ca NPs demonstrated 31-fold higher cellular uptake in Caco-2 cells for 1 h incubation. Furthermore, the transepithelial transport efficiency of Hc@CP-Ca NPs was 12-fold higher than that of free insulin. Moreover, CP-Ca NPs and Hc@CP-Ca NPs generated a rapid-onset and long-lasting hypoglycemic effect following gavage in type 1 diabetic mellitus (T1DM) rats. The pharmacological activity and the relative bioavailability were increased to 13.5% and 12.2%, respectively. Thus, these results indicated that CHP assembled NPs may provide a promising potential for oral insulin delivery by protection and absorption promotion.

Graphical abstract: Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin

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Supplementary files

Article information


Submitted
11 Apr 2020
Accepted
30 May 2020
First published
01 Jun 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin

Y. Ding, Q. Wang, G. Liu, Y. Feng and W. Zhou, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00577K

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