RESUMO
Two derivatives of hyaluronic acid (HA) have been synthesized by atom transfer radical polymerization (ATRP), starting from an ethylenediamino HA derivative (HA-EDA) and by using diethylaminoethyl methacrylate (DEAEMA) as a monomer for polymerization. Both samples, indicated as HA-EDA-pDEAEMA a and b, are able to condense siRNA, as determined by gel retardation assay and resulting complexes show a size and a zeta potential value dependent on polymerization number, as determined by dynamic light scattering measurements. In vitro studies performed on HCT 116 cell line, that over express CD44 receptor, demonstrate a receptor mediated uptake of complexes, regardless of their surface charge.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Vetores Genéticos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico , Proteínas de Neoplasias/metabolismo , Neoplasias , RNA Interferente Pequeno , Linhagem Celular Tumoral , Vetores Genéticos/química , Vetores Genéticos/farmacologia , Humanos , Receptores de Hialuronatos/genética , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapiaRESUMO
A graft copolymer derivative of hyaluronic acid bearing pendant amino and short polymethacrylate portions (HA-EDA-BMP-MANa) has been employed for the production of a pH sensible vancomycin releasing hydrogel and studied in vitro to test its potential anti adhesive property against Staphylococcus aureus colonization. The copolymer obtained through atom transfer radical polymerization bears chargeable (carboxyl and amino groups) portions and it could be formulated as a hydrogel at a concentration of 10%w/v. The HA-EDA-BMP-MANa hydrogels, produced at three different pH values (5, 6 and 7, respectively), were formulated with or without the addition of vancomycin (2%w/v). The vancomycin release profiles were detected and related to the starting hydrogel pH values, demonstrating that the systems were able to sustain the release of drug for more than 48 h. S. aureus adhesion tests were performed on glass culture plates and hydroxyapatite doped titanium surfaces, comparing the performances of HA-EDA-BMP-MANa hydrogel formulations (obtained with and without vancomycin) with similar formulations obtained using unmodified hyaluronic acid. The non fouling property of a selected HA-EDA-BMP-MANa hydrogel (without vancomycin) was also assayed with a BSA adsorption test. We found that the HA-EDA-BMP-MANa hydrogel even without vancomycin prevented bacterial adhesion on investigated surfaces.
