RESUMO
Inulin has been derivatized with methacrylic anhydride (MA) and succinic anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model made by unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) was investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC) that appears to be a suitable technique to follow the transfer kinetics of a drug from a controlled release system to a biomembrane model. The drug release from the hydrogel was compared with the dissolution of drug solid form by examining the effects exerted on the thermotropic behaviour of the DMPC unilamellar vesicles. The transferred drug and the release rate were affected by the drug loading as well as by the pH of the external medium. In particular the release was not linearly related to the drug loading but an intermediate loading allowed a better release at both investigated pHs, with a faster and more complete release observed at pH 7.4.
Assuntos
Hidrogéis/química , Hipoglicemiantes/administração & dosagem , Inulina/química , Membranas Artificiais , Anti-Inflamatórios não Esteroides/química , Varredura Diferencial de Calorimetria , Centrifugação , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Diflunisal/química , Dimiristoilfosfatidilcolina/química , Concentração de Íons de Hidrogênio , Hipoglicemiantes/química , Insulisina/química , Espectroscopia de Ressonância Magnética , Peso Molecular , Solubilidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Succinatos/química , Difração de Raios XRESUMO
A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimicking biological fluids. The possibility to employ the prepared hydrogel as a pH-sensitive drug delivery system (DDS) has been investigated. In particular, ibuprofen ((S)(+)4-isobutyl-alpha-methylphenyl-acetic acid), chosen as a model drug, has been entrapped into the PHM-SA hydrogel, and in vitro release studies have showed that its release rate depends on different swelling of the network as a function of the environmental pH.