Preparation and characterization of self-assembled nanoparticles of heparin-deoxycholic acid conjugates.
Various deoxycholic acid (DOCA) bearing heparin (HD) amphiphilic conjugates with different degrees of substitution (DS) with DOCA were synthesized using heparin as a hydrophilic segment and DOCA as a hydrophobic segment. Structural characteristics of these HD conjugates were investigated using 1H NMR, dynamic light scattering, zeta potential, transmission electron microscopy (TEM), and fluorescence spectroscopy. HD conjugates provided monodispersed self-aggregates in water, with mean diameters decreasing with increasing DOCA DS in the range of 120-200 nm. HD aggregates were covered with negatively charged heparin shells, exhibiting xi potentials near -56 mV. The critical aggregation concentration (cac) of the HD (0.02-0.003 mg/mL) depended upon DOCA DS. TEM images demonstrated that the shape of the self-aggregates was spherical. Partition equilibrium constants, Kv, for pyrene in the self-aggregates in water indicated that increasing DS enhanced the hydrophobicity of the self-aggregate inner core. The mean aggregation number of DOCA per hydrophobic microdomain, estimated by the fluorescence quenching methods using cetylpyridinium chloride, indicated that five to nine of HD chains comprised a hydrophobic domain in the conjugates.
Park
Kyeongsoon
K
Center for Cell and Macromolecular Therapy, Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 1 Oryong-dong Puk-gu Gwangju 500-712, Korea.
Kim
Kwangmeyung
K
Kwon
Ick Chan
IC
Kim
Sang Kyoon
SK
Lee
Seulki
S
Lee
Dong Yun
DY
Byun
Youngro
Y
D003840:Deoxycholic Acid / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry* / Q000648:ultrastructure; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D013050:Spectrometry, Fluorescence
D003840:Deoxycholic Acid; D006493:Heparin