Development of delivery methods for carbohydrate-based drugs: controlled release of biologically-active short chain fatty acid-hexosamine analogs.
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 'Bu(4)ManNAc', 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-Bu(3)ManNAc) 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.
Aich
Udayanath
U
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Meledeo
M Adam
MA
Sampathkumar
Srinivasa-Gopalan
SG
Fu
Jie
J
Jones
Mark B
MB
Weier
Christopher A
CA
Chung
Sung Yun
SY
Tang
Benjamin C
BC
Yang
Ming
M
Hanes
Justin
J
Yarema
Kevin J
KJ
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003652:Decanoic Acids / Q000737:chemistry; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005232:Fatty Acids, Volatile / Q000737:chemistry*; D006595:Hexosamines / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry
D000970:Antineoplastic Agents; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D005232:Fatty Acids, Volatile; D006595:Hexosamines; D011145:Polyvinyls; C013215:polyvinyl acetate; D011092:Polyethylene Glycols; C011107:sebacic acid; C002022:N-acetylmannosamine
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