Revealing the interaction between peptide drugs and permeation enhancers in the presence of intestinal bile salts.

Hossain S, Kneiszl R, Larsson P

Nanoscale7 Dec 2023Cited by 12 (Europe PMC)

PMID37982184DOI10.1039/d3nr05571jPepBankPUB-37982184

Summary

Permeability enhancer-based formulations offer a promising approach to enhance the oral bioavailability of peptides. We used all-atom molecular dynamics simulations to investigate the interaction between two permeability enhancers (sodium caprate, and SNAC), and four different peptides (octreotide, hexarelin, degarelix, and insulin), in the presence of taurocholate, an intestinal bile salt. The permeability enhancers exhibited distinct effects on peptide release based on their properties, promoting hydrophobic peptide release while inhibiting water-soluble peptide release. Lowering peptide concentrations in the simulations reduced peptide-peptide interactions but increased their interactions with the enhancers and taurocholates. Introducing peptides randomly with enhancer and taurocholate molecules yielded dynamic molecular aggregation, and reduced peptide-peptide interactions and hydrogen bond formation compared to peptide-only systems. The simulations provided insights into molecular-level interactions, highlighting the specific contacts between peptide residues responsible for aggregation, and the interactions between peptide residues and permeability enhancers/taurocholates that are crucial within the mixed colloids. Therefore, our results can provide insights into how modifications of these critical contacts can be made to alter drug release profiles from peptide-only or mixed peptide-PE-taurocholate aggregates. To further probe the molecular nature of permeability enhancers and peptide interactions, we also analyzed insulin secondary structures using Fourier transform infrared spectroscopy. The presence of SNAC led to an increase in β-sheet formation in insulin. In contrast, both in the absence and presence of caprate, α-helices, and random structures dominated. These molecular-level insights can guide the design of improved permeability enhancer-based dosage forms, allowing for precise control of peptide release profiles near the intended absorption site.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Hexarelin.

01Computer modelNot a test of Hexarelin aloneIn silicoMechanism
In molecular dynamics simulations of four peptides (including hexarelin), the permeability enhancers promoted release of hydrophobic peptides and inhibited release of water-soluble peptides.
In plain wordsIn computer simulations of four peptides, the enhancers helped release of water-repelling peptides and slowed release of water-soluble ones.
Peptide
Hexarelin
Outcome
MixedPeptide release with permeability enhancers (pooled peptides)
Study
n: not reported in source
All-atom molecular dynamics simulations with permeability enhancers and taurocholate
Outcome group
Formulation, delivery and stability · Pharmacology
Source sentences
Summary
The permeability enhancers exhibited distinct effects on peptide release based on their properties, promoting hydrophobic peptide release while inhibiting water-soluble peptide release.
1 context sentence(design, population, supporting numbers)
Summary · context
We used all-atom molecular dynamics simulations to investigate the interaction between two permeability enhancers (sodium caprate, and SNAC), and four different peptides (octreotide, hexarelin, degarelix, and insulin), in the presence of taurocholate, an intestinal bile salt.
In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Hexarelin.
Show in the study text Report a problemFND-3798218401
02Computer modelNot a test of Hexarelin aloneIn silicoMechanism
In molecular dynamics simulations of four peptides (including hexarelin), lower peptide concentrations reduced peptide-peptide interactions but increased interactions with enhancers and taurocholates.
In plain wordsIn computer simulations of four peptides, lower peptide concentrations meant fewer peptide-peptide contacts and more contacts with the enhancers and bile salt.
Peptide
Hexarelin
Outcome
MixedPeptide-peptide interactions at lower peptide concentration (pooled peptides)
Study
n: not reported in source
All-atom molecular dynamics simulations with permeability enhancers and taurocholate
Outcome group
Formulation, delivery and stability · Pharmacology
Source sentences
Summary
Lowering peptide concentrations in the simulations reduced peptide-peptide interactions but increased their interactions with the enhancers and taurocholates.
1 context sentence(design, population, supporting numbers)
Summary · context
We used all-atom molecular dynamics simulations to investigate the interaction between two permeability enhancers (sodium caprate, and SNAC), and four different peptides (octreotide, hexarelin, degarelix, and insulin), in the presence of taurocholate, an intestinal bile salt.
In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Hexarelin.
Show in the study text Report a problemFND-3798218402
03Computer modelNot a test of Hexarelin aloneIn silicoMechanism
In molecular dynamics simulations of four peptides (including hexarelin), adding enhancer and taurocholate gave dynamic molecular aggregation and reduced peptide-peptide interactions and hydrogen bond formation compared with peptide-only systems.
In plain wordsIn computer simulations of four peptides, adding enhancer and bile salt reduced peptide-peptide contacts compared with peptide-only systems.
Peptide
Hexarelin
Outcome
DecreaseAggregation and hydrogen bonding with enhancer and taurocholate (pooled peptides)
Study
n: not reported in source
All-atom molecular dynamics simulations with permeability enhancers and taurocholate
Outcome group
Formulation, delivery and stability · Pharmacology
Source sentences
Summary
Introducing peptides randomly with enhancer and taurocholate molecules yielded dynamic molecular aggregation, and reduced peptide-peptide interactions and hydrogen bond formation compared to peptide-only systems.
1 context sentence(design, population, supporting numbers)
Summary · context
We used all-atom molecular dynamics simulations to investigate the interaction between two permeability enhancers (sodium caprate, and SNAC), and four different peptides (octreotide, hexarelin, degarelix, and insulin), in the presence of taurocholate, an intestinal bile salt.
In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Hexarelin.
Show in the study text Report a problemFND-3798218403

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
27 Oct 2026, 16:34 UTC
Study data updated · source update from Europe PMC
Version 2
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Journal Article

MeSH terms

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