Intestinal permeation enhancers enable oral delivery of macromolecules up to 70 kDa in size
| Autor: | Katherine C, Fein, John P, Gleeson, Alexandra N, Newby, Kathryn A, Whitehead |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
0303 health sciences
Macromolecular Substances Administration Oral Pharmaceutical Science Biological Transport General Medicine 030226 pharmacology & pharmacy Permeability Piperazines Mice 03 medical and health sciences 0302 clinical medicine Intestinal Absorption Animals Humans Caco-2 Cells Adjuvants Pharmaceutic Deoxycholic Acid 030304 developmental biology Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 170:70-76 |
| ISSN: | 0939-6411 |
| Popis: | The decades-long effort to deliver peptide drugs orally has resulted in several clinically successful formulations. These formulations are enabled by the inclusion of permeation enhancers that facilitate the intestinal absorption of peptides. Thus far, these oral peptide drugs have been limited to peptides less than 5 kDa, and it is unclear whether there is an upper bound of protein size that can be delivered with permeation enhancers. In this work, we examined two permeation enhancers, 1-phenylpiperazine (PPZ) and sodium deoxycholate (SDC), for their ability to increase intestinal transport of a model macromolecule (FITC-Dextran) as a function of its size. Specifically, the permeability of dextrans with molecular weights of 4, 10, 40, and 70 kDa was assessed in an in vitro and in vivo model of the intestine. In Caco-2 monolayers, both PPZ and SDC significantly increased the permeability of only FD4 and FD10. However, in mice, PPZ and SDC behaved differently. While SDC improved the absorption of all tested sizes of dextrans, PPZ was effective only for FD4 and FD10. This work is the first report of PPZ as a permeation enhancer in vivo, and it highlights the ability of permeation enhancers to improve the absorption of macromolecules across a broad range of sizes relevant for protein drugs. |
| Databáze: | OpenAIRE |
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