Stereoisomer-Dependent Membrane Association and Capacity for Insulin Delivery Facilitated by Penetratin

Ditlev Birch, Edward J Sayers, Malene V Christensen, Arwyn T Jones, Henrik Franzyk, Hanne M Nielsen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

3 Citationer (Scopus)
12 Downloads (Pure)

Abstract

Cell-penetrating peptides (CPPs), such as penetratin, are often investigated as drug delivery vectors and incorporating d-amino acids, rather than the natural l-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-l and all-d 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 d-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 l-PEN did not increase the transepithelial permeation of any of the investigated cargo peptides, d-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 d-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 l-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.

OriginalsprogEngelsk
Artikelnummer1672
TidsskriftPharmaceutics
Vol/bind15
Udgave nummer6
Antal sider15
ISSN1999-4923
DOI
StatusUdgivet - 2023

Bibliografisk note

his article belongs to the Special Issue Current State of the Field of Cell-Penetrating Peptides as an Honorific Issue for Professor Ülo Langel.

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