Preparation of Sodium Deoxycholate (DOC) Conjugated Heparin Derivatives for Inhibition of Angiogenesis and Cancer Cell Growth

Department of Otolaryngology, Head and Neck Surgery, The Catholic University of Korea, College of Medicine Uijeongbu, St. Mary's Hospital, Kyunggi-Do 480-717, Korea.
Bioconjugate Chemistry (Impact Factor: 4.51). 08/2008; 19(7):1346-51. DOI: 10.1021/bc800173m
Source: PubMed


We describe new DOC (sodium deoxycholate)-heparin nanoparticles for in vivo tumor targeting and inhibition of angiogenesis based on chemical conjugation and the enhanced permeability and retention (EPR) effect. Heparin has been used as a potent anticoagulant agent for 70 years, and has recently been found to inhibit the activity of growth factors which stimulate the smooth muscle cells around tumor. From the results, DOC and heparin were conjugated by bonding carboxyl groups of heparin with amine groups of aminated sodium deoxycholate. Larger antitumor effects of the DOC-heparin VI (8.5 mol of DOC coupled with 1.0 mol heparin) were achieved in animal studies, compared to heparin alone. We confirmed that the conjugated heparin retained its ability to inhibit binding with angiogenic factor, showing a significant decrease in endothelial tubular formation. These results provide new insights into the nontoxic anticancer drug carrier as well as the design of multifunctional bioconjugates for targeted drug delivery.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Demand for solar power in the commercial rooftop market sector is growing at a very rapid rate. Overall, the grid-connected market exceeded 50% of the roughly 320 MWp, photovoltaic (PV) market in 2001, continuing a dramatic trend from just 10 years ago when grid-connected systems were an insignificant fraction of the total market. PowerLight Corporation, the nation's leading integrator and installer of grid-connected commercial PV systems, just completed its fifth year of doubled annual growth, and during the first quarter of 2002 increased its manufacturing capacity of PowerGuard roof tiles to 20 megawatts per year. PowerLight's commercial rooftop systems installed to date range from 5 kW to over 1 MW, and the average system size has increased to well over 100 kW. Improved system costs along with aggressive Federal and State incentives have helped to make these PV systems economic for commercial and industrial customers. PowerLight continues to design, integrate and install other types of grid-connected arrays.
    No preview · Conference Paper · Jun 2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The oral delivery of heparin is the preferred therapy in the treatment of patients with a high risk of deep vein thrombosis and pulmonary embolism. New conjugates of heparin and sodium deoxycholate were synthesized in order to enhance the heparin absorption in the GI tract. After oral administration of DOC-heparin, the concentration in anti-FXa assay was increased with increasing amount of coupled DOC. The maximum concentration of DOC-heparin VIII conjugate was 3.3±0.5 IU/mL at an oral dose of 10 mg/kg, which was 3-fold higher than the base-line level. Finally, DOC coupled to heparin greatly enhanced the absorption of heparin in the GI tract, and this enhancing effect was not induced by changing the tissue structure of the GI wall. Keywordssodium deoxycholate–oral delivery–heparin–conjugate
    Preview · Article · Feb 2009 · Macromolecular Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel kind of chitosan derivatives (CS-LA-TM) were synthesized by grafting hydrophobic molecules of lithocholic acid (LA) and quaternization. CS-LA-TM and micelle-like self-aggregates were characterized by FTIR, 1H NMR, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). The critical micelles concentration (CMC) ranging from 0.009 mg/mL to 0.030 mg/mL decreased with increasing of the degree of substitution (DS) of LA, pH of medium but with decreasing of the degree of quaternization (DQ) of amino groups. The TEM images demonstrated that spherical CS-LA-TM nanoaggregates with uniform size were formed by self-assembly. The sizes (100-200 nm) of CS-LAs-TMs nanoaggregates increased with increasing of DS, DQ, and can be easily controlled by pH of medium, which may confer the nanoaggregates potential as delivery systems for anticancer drugs, or DNA and siRNA.
    No preview · Article · Apr 2010 · Journal of Nanoscience and Nanotechnology
Show more