TY - JOUR
T1 - Development of delivery methods for carbohydrate-based drugs
T2 - Controlled release of biologically-active short chain fatty acid-hexosamine analogs
AU - Aich, Udayanath
AU - Meledeo, M. Adam
AU - Sampathkumar, Srinivasa Gopalan
AU - Fu, Jie
AU - Jones, Mark B.
AU - Weier, Christopher A.
AU - Chung, Sung Yun
AU - Tang, Benjamin C.
AU - Yang, Ming
AU - Hanes, Justin
AU - Yarema, Kevin J.
N1 - Funding Information:
Acknowledgments Funding for this project was provided by the National Institutes of Health (CA11231404) for SCFA-hexosamine synthesis and analysis of anti-metastatic responses in MDA-MB-231 cells, (EB005692-03 for synthesis and evaluation of sebacic acid-PEG polymers), and the Johns Hopkins Institute for NanoBioTechnology (INBT, for the synthesis and biological evaluation of the covalently-conjugated nanoparticles).
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Carbohydrate drug delivery
KW - Microparticles
KW - Nanoparticles
KW - PEG-SA polymer
KW - SCFA-hexosamine analogs
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U2 - 10.1007/s10719-010-9292-3
DO - 10.1007/s10719-010-9292-3
M3 - Article
C2 - 20458533
AN - SCOPUS:77955653580
SN - 0282-0080
VL - 27
SP - 445
EP - 459
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 4
ER -