Aiming for glycolipid-based vesicles for targeted drug delivery, cationic Guerbet glycosides with spacered click functionality were designed and synthesized. The cationic charge promoted the distribution of the glycolipids during the formulation, thereby leading to homogeneously small vesicles. The positive surface charge of the vesicles stabilizes them against unwanted fusion and promotes interactions of the drug carriers with typical negative charge-dominated target cells. High bioconjugation potential of the functionalized glycolipids based on the copper-catalyzed azide alkyne cycloaddition makes them highly valuable components for targeted drug delivery systems.
Two azide-terminated oligoethylene oxide spacered glycolipids have been synthesized, and their assembly behavior has been studied in comparison to the corresponding base surfactants. The results suggest potential of the Guerbet lactoside-based compound for targeted drug delivery, while a coiling of the ethylene oxide linker disfavors the application of the glucoside.
A new synthesis approach towards biantennary lipids of Guerbet glycoside type was developed based on oleic acid as sustainable resource. Functionalization of the double bond provided access to primary alcohols with α-branched C19-skeleton. Formulation studies with corresponding lactosides indicated formation of vesicles with high assembly stability. A relatively narrow bimodal size distribution of the latter, which turns into a narrow unimodal distribution of small vesicles upon addition of an ionic cosurfactant, suggests potential for a vesicular drug delivery system.