Temperature and polymer crosslinking degree influence on drug transfer from α,β-polyasparthydrazide hydrogel to model membranes. A calorimetric study
A non-steroidal anti-inflammatory drug, diflunisal, has been chosen as drug model to be incorporated in α,β-polyasparthydrazide (PAHy) matrices to study the effect of polymer crosslinking degrees on the release processes from hydrogel (X=0.4 and X=0.8) to a model membrane represented by unilamellar vesicles of dipalmitoylphosphatidylcholine. The technique employed to monitor these processes was differential scanning calorimetry that appears to be particularly suitable to follow the transfer kinetics of a drug from a controlled release system to void biomembrane model. The drug release from the two PAHy hydrogels differently crosslinked by glutaraldehyde to the lipidic model was compared with that from the drug solid form, by examining the effects exerted on the thermotropic behaviour of unilamellar vesicles. The diflunisal (DFN) is able to interact with unilamellar vesicles by causing a decrease of the transitional (gel-to-liquid crystal phase transition) temperature characteristic of lipidic bilayer. The amount of DFN transferred and interacting with the dipalmitoylphosphatidylcholine (DPPC) unilamellar vesicles was quantified by comparing the effects caused on the thermodynamic parameters of bilayer (transitional temperature, Tm, and enthalpy variation, ΔH) with the effects obtained from increasing molar fractions of drug. The release kinetics of the drug from PAHy hydrogels were followed at different temperatures (25, 37 and 50°C) to determine the influence of temperature on the drug release and successive transfer at a biological membrane. Particularly, it appears evident that by increasing the polymer crosslinking degree the total amount of transferred drug and the release velocity are decreased. This behavior may be caused by the increase of the number of cruciate bonds in the hydrogels, which causes a free volume reduction obstructing the drug passing. The obtained results suggest that PAHy hydrogels constitute an innovative delivery system able to slightly release water-soluble drugs and to modulate their uptake by biomembrane.
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