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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
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Neo-Glycolipid Oximes as Intestinal Permeation Enhancers for Peptide Hormone PYY3-36
Panagiota Kalomoiri1,2, Janni S Mortensen3,2, Niels Johan Christensen1,2
1Department of Chemistry, University of Copenhagen, Thorvaldsensvej 40, DK-1871, Frederiksberg, Denmark.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|November 6, 2024
Summary
New neo-glycolipids enhance oral drug delivery by increasing intestinal permeation. These compounds show promise for delivering peptide therapeutics, including for obesity treatments, with good cellular compatibility.
Area of Science:
- Biochemistry
- Pharmaceutics
- Drug Delivery
Background:
- Oral delivery of peptide therapeutics is challenging due to poor intestinal permeation.
- Novel permeation enhancers are needed to improve the bioavailability of peptide drugs.
Purpose of the Study:
- To design, synthesize, and evaluate novel neo-glycolipids as permeation enhancers for oral drug delivery.
- To assess the efficacy of neo-glycolipids in enhancing the permeation of model compounds and a peptide hormone across intestinal epithelium.
Main Methods:
- Synthesis of 16 amphiphilic neo-glycolipids composed of fatty acids and carbohydrates.
- In vitro evaluation of permeation enhancement using Caco-2 cell monolayers with fluorescein-labelled dextran and 3H-mannitol.
- Comparison with known enhancers like sodium salts of fatty acids and sodium salcaprozate (SNAC).
- Assessment of neo-glycolipids for enhancing peptide hormone PYY3-36 permeation.
Main Results:
- Most synthesized neo-glycolipids effectively enhanced the permeation of model compounds across Caco-2 cell monolayers.
- Neo-glycolipids demonstrated different properties (e.g., clogD, polar surface area) compared to reference compounds, yet proved effective.
- A neo-glycolipid derived from decanoic acid and glucose showed higher potency than those based on disaccharides.
- Neo-glycolipids based on decanoic and dodecanoic acids, derived from glucose and maltose, significantly enhanced PYY3-36 permeation in vitro with good cellular compatibility.
Conclusions:
- Neo-glycolipids are effective permeation enhancers for oral drug delivery.
- Specific neo-glycolipids show potential for enhancing the oral delivery of peptide therapeutics, including PYY3-36 for obesity treatments.
- The choice of carbohydrate moiety influences neo-glycolipid solubility and cellular compatibility, impacting their suitability for drug delivery applications.
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