1. Neo‐Glycolipid Oximes as Intestinal Permeation Enhancers for Peptide Hormone PYY3‐36.
- Author
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Kalomoiri, Panagiota, Mortensen, Janni S., Christensen, Niels Johan, Sørensen, Kasper K., Nielsen, Hanne Mørck, Jensen, Knud J., and Thygesen, Mikkel B.
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SODIUM compounds ,INTESTINAL mucosa ,PEPTIDE hormones ,DECANOIC acid ,DEXTRAN ,GLYCOLIPIDS - Abstract
Herein, we describe the design and synthesis of 16 neo‐glycolipids that are potential permeation enhancers for oral drug delivery of peptide therapeutics. These amphiphilic neo‐glycolipids are composed of fatty acids and various carbohydrates (d‐glucose, lactose, cellobiose, maltose) via an oxime linker. The ability of the synthesized neo‐glycolipids to enhance permeation of fluorescein‐labelled dextran (4 kDa) or 3H‐mannitol across intestinal epithelium was investigated in vitro using monolayers of human epithelial Caco‐2 cells. Their effects were compared with (pre‐)clinically known enhancers as reference compounds; sodium salts of octanoic, decanoic, and dodecanoic acid, and sodium salcaprozate (SNAC). Most neo‐glycolipids increased the permeation of the model compounds, proving that neo‐glycolipids, which possess vastly different properties from the reference compounds, e. g. in terms of clogD and polar surface area, are effective permeation enhancers. The neo‐glycolipid based on decanoic acid and glucose was more potent than related compounds based on disaccharides. Significant differences in solubility and cellular compatibility were found for neo‐glyolipids based on different carbohydrates. Finally, neo‐glycolipids were evaluated as permeation enhancers for the peptide hormone PYY3‐36. Glucose‐ and maltose‐derived neo‐glycolipids based on decanoic and dodecanoic acid showed promising enhancements in PYY3‐36 permeation in vitro while maintaining good cellular compatibility, relevant for oral delivery of obesity treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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