Stereoisomer-Dependent Membrane Association and Capacity for Insulin Delivery Facilitated by Penetratin
Cell-penetrating peptides (CPPs), such as penetratin, are often investigated as drug delivery vectors and incorporating <span style="font-variant: small-caps;">d</span>-amino acids, rather than the natural <span style="font-variant: small-caps;">l</span>-f...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Book |
| Published: |
MDPI AG,
2023-06-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Cell-penetrating peptides (CPPs), such as penetratin, are often investigated as drug delivery vectors and incorporating <span style="font-variant: small-caps;">d</span>-amino acids, rather than the natural <span style="font-variant: small-caps;">l</span>-forms, to enhance proteolytic stability could improve their delivery efficiency. The present study aimed to compare membrane association, cellular uptake, and delivery capacity for all-<span style="font-variant: small-caps;">l</span> and all-<span style="font-variant: small-caps;">d</span> enantiomers of penetratin (PEN) by using different cell models and cargos. The enantiomers displayed widely different distribution patterns in the examined cell models, and in Caco-2 cells, quenchable membrane binding was evident for <span style="font-variant: small-caps;">d</span>-PEN in addition to vesicular intracellular localization for both enantiomers. The uptake of insulin in Caco-2 cells was equally mediated by the two enantiomers, and while <span style="font-variant: small-caps;">l</span>-PEN did not increase the transepithelial permeation of any of the investigated cargo peptides, <span style="font-variant: small-caps;">d</span>-PEN increased the transepithelial delivery of vancomycin five-fold and approximately four-fold for insulin at an extracellular apical pH of 6.5. Overall, while <span style="font-variant: small-caps;">d</span>-PEN was associated with the plasma membrane to a larger extent and was superior in mediating the transepithelial delivery of hydrophilic peptide cargoes compared to <span style="font-variant: small-caps;">l</span>-PEN across Caco-2 epithelium, no enhanced delivery of the hydrophobic cyclosporin was observed, and intracellular insulin uptake was induced to a similar degree by the two enantiomers. |
|---|---|
| Item Description: | 10.3390/pharmaceutics15061672 1999-4923 |