Development of delivery methods for carbohydrate-based drugs: Controlled release of biologically-active short chain fatty acid-hexosamine analogs

Udayanath Aich, M. Adam Meledeo, Srinivasa Gopalan Sampathkumar, Jie Fu, Mark B. Jones, Christopher A. Weier, Sung Yun Chung, Benjamin C. Tang, Ming Yang, Justin Hanes, Kevin J. Yarema

Research output: Contribution to journalArticle

Abstract

Carbohydrates are attractive candidates for drug development because sugars are involved in many, if not most, complex human diseases including cancer, immune dysfunction, congenital disorders, and infectious diseases. Unfortunately, potential therapeutic benefits of sugar-based drugs are offset by poor pharmacologic properties that include rapid serum clearance, poor cellular uptake, and relatively high concentrations required for efficacy. To address these issues, pilot studies are reported here where 'Bu4ManNAc', a short chain fatty acid-monosaccharide hybrid molecule with anti-cancer activities, was encapsulated in polyethylene glycol-sebacic acid (PEG-SA) polymers. Sustained release of biologically active compound was achieved for over a week from drug-laden polymer formulated into microparticles thus offering a dramatic improvement over the twice daily administration currently used for in vivo studies. In a second strategy, a tributanoylated ManNAc analog (3,4,6-O-Bu3ManNAc) with anti-cancer activities was covalently linked to PEG-SA and formulated into nanoparticles suitable for drug delivery; once again release of biologically active compound was demonstrated.

Original languageEnglish (US)
Pages (from-to)445-459
Number of pages15
JournalGlycoconjugate Journal
Volume27
Issue number4
DOIs
StatePublished - May 1 2010

Keywords

  • Carbohydrate drug delivery
  • Microparticles
  • Nanoparticles
  • PEG-SA polymer
  • SCFA-hexosamine analogs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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