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

Abstract

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.

Keywords::

• Hyaluronic acid
• polylactic acid
• polyethylenglycol
• micelles
• selective cytotoxicity

Acknowledgements

This work has been financially supported by MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca) grants. TEM experimental data were provided by “Centro Grandi Apparecchiature—UniNetLab—Universita’ di Palermo funded by P.O.R. Sicilia 2000-2006, Misura 3.15 Quota regionale.”

Declaration of interest: There is no conflit of interest between authors and MIUR.