Oral self-emulsifying delivery systems for systemic administration of therapeutic proteins: science fiction?

Abstract

Objective: The aim of this study was to develop self-emulsifying drug delivery systems (SEDDS) for oral delivery of therapeutic proteins through hydrophobic ion pairing.

Method: Horseradish peroxidase (HRP), a model protein, was ion paired with sodium docusate to increase its hydrophobicity. The formed enzyme - surfactant complex was incorporated into SEDDS, followed by permeation studies across Caco-2 cell monolayer and freshly excised rat intestine.

Results: Hydrophobic ion pairs (HIP) were formed between HRP and sodium docusate with the efficiency of 87.49 ± 1.35%. The formed complex maintained 60.97 ± 1.48% of the original enzyme activity. The ion pair was subsequently loaded into SEDDS with a payload of 0.1% (mass per cent, m/m). The obtained emulsion formed by SEDDS had a droplet size in the range from 20 to 200 nm with negative zeta potential. Permeation mechanism of the enzyme was energy-dependent and the encapsulation of the HIP complex in SEDDS enhanced the permeation of the enzyme through the Caco-2 cell monolayer and freshly excised rat intestine by 4 times and 2.5 times compared to the free enzyme, respectively.

Conclusion: According to these findings, hydrophobic ion pairing followed by incorporation to SEDDS might be considered as a potential strategy for oral delivery of therapeutic proteins.

Keywords:

• Hydrophobic ion pairing
• protein delivery
• self-emulsifying drug delivery system
• horseradish peroxidase

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by Technology Grants South East Asia financed by the Austrian Federal Ministry for Science and Research and administered/executed by the OeAD (Austrian Agency for International Cooperation in Education and Research, OeAD-GmbH).