Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

• Published in: Pharmaceutics 2021-12, Vol.14 (1), p.39
• Main Authors: Reboredo, Cristian, González-Navarro, Carlos J, Martínez-López, Ana Luisa, Martínez-Ohárriz, Cristina, Sarmento, Bruno, Irache, Juan M
• Format: Article
• Language: English
• Subjects: Bioavailability; Ethanol; Insulin; Molecular weight; mucus-permeating; Nanoparticles; oral delivery; Peptides; poly(ethylene glycol); Proteins; Sodium; zein
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14010039

Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In , where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.