Synthesis of Glycolipid-based Drug Delivery Systems for Oral Administration

Background and Objective: Many recent studies have focused on the development of methods to overcome the barriers faced by oral drug delivery. This study describes the synthesis of three glycolipid-based drug delivery systems designed to be associated with charged drugs to improve their oral bioavailability. Methods: D-Glucose was used as a scaffold to construct charged glycolipids with anionic and/or cationic properties. Three glycolipids with positive and negative functionalities were designed, synthesized by various carbohydrate, lipid and Bocchemistry methods. The products were purified by flash column chromatography and characterized by ESI-MS and NMR. Results: The first glycolipid was synthesized by complete lipidation of D-glucose using lipoamino acids with positively charged amino groups. The negatively charged glycolipid was obtained by coupling succinate bearing a free carboxylic group to lauroylated glucose. Combining both strategies, the target compound, which can bear either positive or negative charges, was prepared through the conjugation of succinate to the carbohydrate core followed by the addition of lipoamino acids. Separation of the compounds from impurities (not fully lapidated derivatives) by flash column chromatography proved to be challenging. Conclusion: Ensuring the purity of all semi-products used in each reaction was paramount to prevent complicated purification of the final compounds. Once the three glycolipids were carefully purified, protecting groups were cleaved to give cationic and anionic properties. These glycolipids can undergo complexation with charged drugs to improve their oral bioavailability. This system has the potential to serve as a universal template for oral drug delivery.