Antonella Albanese

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.

In situ forming hydrogels of new amino hyaluronic acid/benzoyl-cysteine derivatives as potential scaffolds for cartilage regeneration

A new chemical strategy is described to link ethylenediamino (EDA) groups to primary hydroxyl groups of hyaluronic acid (HA) and the obtained derivatives have been characterized by 1H-NMR and 13C-NMR analyses. Such HA–EDA derivatives have been exploited to control the functionalization degree in benzoyl-cysteine (BC) groups, chosen as moieties able to allow both self-assembling in aqueous media and an oxidative crosslinking. In particular, the kinetics of oxidation of thiol groups in HA–EDA–BC derivatives has been studied in Dulbeccos Phosphate Buffer Solution (DPBS) pH 7.4 by colorimetric assays and rheological measurements. Mechanical properties of chemical hydrogels obtained after oxidative crosslinking have been evaluated by using two different concentration values (1 and 1.5% w/v) of HA–EDA–BC. These hydrogels show a dense interconnected fibrillar structure similar to the extracellular matrix of soft tissue and a resistance to chemical and enzymatic hydrolysis. Therefore, the potential suitability of HA–EDA–BC hydrogels as scaffolds for cartilage regeneration has been preliminarily assessed using primary human chondrocytes and evaluating their viability and ability to produce extracellular collagen.