Self-assembled hydrogel nanoparticles from curdlan derivatives: characterization, anti-cancer drug release and interaction with a hepatoma cell line (HepG2)

Self-assembled hydrogel nanoparticles were synthesized from carboxymethylat ed (CM)-curdian, substituted with a sulfonylurea (SU) as a hydrophobic moie ty for self-assembly. The degree of SU substitution was 2.4, 5.6, or 7.2 SU groups per hundred anhydroglucose units of curdlan. The physicochemical pr operties of the self-assembled hydrogel nanoparticles (DS 2.4, DS 5.6, and DS 7.2) in aqueous media were characterized by dynamic light scattering, tr ansmission electron microscopy, and fluorescence spectroscopy. The mean dia meter of all samples was less than 300 nm with a unimodal size distribution . The critical aggregation concentrations (CAC) of self-assembled hydrogel nanoparticles in distilled water were 4.2x10(-2), 3.1x10(-2) and 1.9x10(-2) mg/ml for DS 2.4, 5.6 and 7.2, respectively. The loading and release of al l-trans retinoic acid (ATRA) was studied. The ATRA loading efficiencies and loading contents of CM-curdlan/SU nanoparticles increased as the degree of SU substitution increased. The ATRA release rate was controlled by the deg ree of substitution and drug-loading. For specific interaction with a hepat ic carcinoma cell line (HepG2), CM-curdlan was additionally conjugated with lactobionic acid (LBA; galactose moiety) (5.5 LBA molecules per hundred gl ucose units). HepG2 was strongly luminated by ligand-receptor interactions with fluorescence-labeled LBA/CM-curdlan/SU hydrogel nanoparticles. The lum inescence was not observed for other control cases. It is concluded that LB A/CM-curdlan/SU hydrogel nanoparticles are a useful drug carrier for the tr eatment of liver cancer, because of the potential immunological enhancement activities of CM-curdlan in the body, the ligand-receptor mediated specifi c interactions, and the controlled release of the anti-cancer drug. (C) 200 0 Elsevier Science B.V. AU rights reserved.