Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content. (C) 2002 Elsevier Science B.V. All rights reserved.