Gels obtained by complexation of octablock star polyethylene oxide/polypropylene oxide copolymers (Tetronic 90R4) with α‐cyclodextrin (α‐CD) were evaluated as matrices for drug release. Both molecules are biocompatible so they can be potentially applied to drug delivery systems. Two different types of matrices of Tetronic 90R4 and α‐CD were evaluated: gels and tablets. These gels are capable to gelifying in situ and show sustained erosion kinetics in aqueous media. Tablets were prepared by freeze‐drying and comprising the gels. Using these two different matrices, the release of two model molecules, L‐tryptophan (Trp), and a protein, bovine serum albumin (BSA), was evaluated. The release profiles of these molecules from gels and tablets prove that they are suitable for sustained delivery. Mathematical models were applied to the release curves from tablets to elucidate the drug delivery mechanism. Good correlations were found for the fittings of the release curves to different equations. The results point that the release of Trp from different tablets is always governed by Fickian diffusion, whereas the release of BSA is governed by a combination of diffusion and tablet erosion. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:197–206, 2014

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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 Caenorhabditis elegans, 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.