Interactions of oral permeation enhancers with lipid membranes in simulated intestinal environments.
Int J Pharm
; 654: 123957, 2024 Apr 10.
Article
in En
| MEDLINE
| ID: mdl-38430950
ABSTRACT
The oral bioavailability of therapeutic peptides is generally low. To increase peptide transport across the gastrointestinal barrier, permeation enhancers are often used. Despite their widespread use, mechanistic knowledge of permeation enhancers is limited. To address this, we here investigate the interactions of six commonly used permeation enhancers with lipid membranes in simulated intestinal environments. Specifically, we study the interactions of the permeation enhancers sodium caprate, dodecyl maltoside, sodium cholate, sodium dodecyl sulfate, melittin, and penetratin with epithelial cell-like model membranes. To mimic the molecular composition of the real intestinal environment, the experiments are performed with two peptide drugs, salmon calcitonin and desB30 insulin, in fasted-state simulated intestinal fluid. Besides providing a comparison of the membrane interactions of the studied permeation enhancers, our results demonstrate that peptide drugs as well as intestinal-fluid components may substantially change the membrane activity of permeation enhancers. This highlights the importance of testing permeation enhancement in realistic physiological environments and carefully choosing a permeation enhancer for each individual peptide drug.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Intestinal Absorption
/
Intestinal Mucosa
Limits:
Humans
Language:
En
Journal:
Int J Pharm
Year:
2024
Document type:
Article
Affiliation country:
Denmark
Country of publication:
Netherlands