Development and characterization of anionic liposaccharides for enhanced oral drug delivery

The aim of this study was to synthesize charged amphoteric molecules, which after complexation with poorly bioavailable drugs would have the potential to improve their oral uptake. Novel anionic liposaccharide derivatives containing d-glucose and lipoamino acids were synthesized by solution phase peptide synthesis. High sensitivity isothermal titration microcalorimetry was used to determine the critical aggregation concentration and the thermodynamic profiles. Hemolytic and cytotoxic activities of the liposaccharides were studied and they revealed that the liposaccharides were non-toxic at the concentration used for oral administration. Mixing a model drug, tobramycin, with the liposaccharide containing two lipids formed aggregates around 200 nm, which increased tobramycin partitioning between n-octanol/water. The results suggested that the studied liposaccharide with two lipids was safe to apply biologically and may have an absorption enhancing activity on hydrophilic, orally poorly available drugs.

Charged liposaccharides 4 and 9 associated with the model drug tobramycin.Figure optionsDownload high-quality image (161 K)Download as PowerPoint slide