Assessing the Utility of In Vitro Screening Tools for Predicting Bio-Performance of Oral Peptide Delivery
In this study we evaluated the utility of in-vitro screening tools for predicting the in-vivo behavior of six cyclic peptides with different solubility and permeability properties (BCS class II and III), intended for oral delivery in presence of permeation enhancer Labrasol.
An in vitro flux assay was used to assess peptide permeation across a biomimetic, lipid-based membrane and in vivo studies in rats were used to determine oral peptide bioavailability in the presence of Labrasol.
The in vitro flux was significantly increased for BCS class III peptides, while it significantly decreased or remained unchanged for BCS class II peptides with increasing Labrasol concentrations. The different flux responses were attributed to the combination of reduced effective free peptide concentration and increased membrane permeability in the presence of Labrasol. In vivo studies in male Wistar-Hans rats indicated improved oral bioavailability at different extents for all peptides in presence of Labrasol. On comparing the in vitro and in vivo data, a potential direct correlation for BCS class III peptides was seen but not for BCS class II peptides, due to lower free concentrations of peptides in this class.
This study assessed the utility of in vitro screening tools for selecting peptides and permeation excipients early in drug product development.
Key wordsflux oral delivery peptides permeation enhancer
Area under the Curve
Biopharmaceutics Classification System
Heteronuclear Multiple Bond Correlation
Heteronuclear Single Quantum Coherence/Correlation Spectroscopy
Nuclear Magnetic Resonance
Nuclear Overhauser Enhancement Spectroscopy
Parallel Artificial Membrane Permeability Assay
Phosphate Buffered Saline
Acknowledgments and Disclosures
This research was performed as a part of MRL Postdoctoral Research Program.
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