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Zein-based nanoparticles for the oral delivery of insulin

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Abstract

The aim of this work was to evaluate oral nanocarriers, prepared from zein nanoparticles coated with a poly(anhydride)-thiamine conjugate (GT), for the delivery of insulin. Nanoparticles displayed a size of 250 nm with a negative surface charge, and an insulin loading of 80 μg/mg. Under simulated gastric conditions, GT-coated nanoparticles released a significantly lower amount of insulin than bare ones; whereas in simulated intestinal conditions, both types of nanoparticles displayed a similar behavior. The effect of insulin on the lipid metabolism of C. elegans under high glucose conditions, characterized by a reduction of the fat content, was also investigated. The effect was significantly higher for the nanoencapsulated forms of insulin than for the free protein (p < 0.001). This effect was two times higher for GT-coated nanoparticles than for bare ones. In rats, the hypoglycemic effect and the pharmacokinetic profile of insulin-loaded nanoparticles orally administered (50 IU/kg) were evaluated. The glycemia of animals slowly decreased reaching a minimum 6–10-h post-administration, with a maximum decrease of about 60%. The pharmacological availability of nanoencapsulated insulin was 13.5%. In serum, nanoparticles provided a maximum of insulin 4-h post-administration, and its relative oral bioavailability was 5.2% (compared with a sc formulation of insulin).

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Funding

The research has received funding from the European Community’s Seventh Framework Programme [FP7/2007-2013] for ALEXANDER under grant agreement no. NMP-2011-1.2-2-280761 and financial support from “Asociación de Amigos” of the University of Navarra.

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  1. NANO-VAC Research Group, Department of Chemistry and Pharmaceutical Technology, University of Navarra, C/Irunlarrea, 1, 31008, Pamplona, Spain

    Laura Inchaurraga, Ana L. Martínez-López, Nekane Martin-Arbella & Juan M. Irache

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  1. Laura Inchaurraga
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Correspondence to Juan M. Irache.

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Inchaurraga, L., Martínez-López, A.L., Martin-Arbella, N. et al. Zein-based nanoparticles for the oral delivery of insulin. Drug Deliv. and Transl. Res. 10, 1601–1611 (2020). https://doi.org/10.1007/s13346-020-00796-3

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