Synthesis of glycolipid-based drug delivery systems for oral administration

Lee, Wan Ling, Toth, Istvan and Simerska, Pavla (2016) Synthesis of glycolipid-based drug delivery systems for oral administration. Drug Delivery Letters, 6 1: 38-45. doi:10.2174/2210303106666160506155139

Author Lee, Wan Ling
Toth, Istvan
Simerska, Pavla
Title Synthesis of glycolipid-based drug delivery systems for oral administration
Journal name Drug Delivery Letters   Check publisher's open access policy
ISSN 2210-304X
Publication date 2016-05-01
Sub-type Article (original research)
DOI 10.2174/2210303106666160506155139
Open Access Status Not yet assessed
Volume 6
Issue 1
Start page 38
End page 45
Total pages 8
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
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Created: Thu, 26 May 2016, 00:48:23 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences