Self-assembled amphiphilic hyaluronic acid graft copolymers for targeted release of antitumoral drug.

Polymeric micelles obtained by self-assembling of amphiphilic hyaluronic acid (HA) graft copolymers have been prepared and characterized. In particular, hyaluronic acid (HA) has been grafted to polylactic acid (PLA) and polyethylenglycol chains (PEG), then the copolymers able to form micelles in aqueous medium have been chosen to entrap the antitumoral drug Doxorubicin. The critical aggregation concentration of HA-g-PLA or HA-g-PLA-g-PEG micelles has been determined by using pyrene as a fluorescent probe, whereas their shape and size have been evaluated by light scattering measurements, scanning and transmission electron microscopies. The selective cytotoxicity of drug loaded micelles toward the CD-44 over-expressing HCT-116 cells compared to receptor deficient human derm fibroblasts has been demonstrated. Pegylated micelles showed better stability and drug loading capacity and they were able to escape from macrophage phagocytosis.