REDOX-SENSITIVE GELATIN NANOHYDROGELS FOR DICLOFENAC RELEASE

According to World Health Organization, cancer is the second cause of death after cardiovascular diseases worldwide1. Besides mortality, the economic impact has been increasing year by year due to higher medical and hospitalization costs. Thus, the development of new medical therapies to treat cancer is necessary. In the present work, gelatin was derivatized by maleic anhydride for further obtaining nanohydrogels. The derivatization steps anchored maleimide groups onto the gelatin backbone, with a grafting degree of 45%. The derivatized gelatin was crosslinked through a Michael-addition reaction between maleimide groups of gelatin and amine groups of cystamine dihydrochloride. The cystamine molecule has a disulfide linkage which shows sensitive responsiveness to reduced glutathione expressed in cancer cells2. The structural modification and crosslinking of samples were evaluated by H NMR, FTIR, and size exclusion chromatography. The derivatized gelatin was crosslinked in an inverse emulsion system for obtaining nanohydrogels. Adjusting the surfactant concentration, it was possible to obtain particles with hydrodynamic diameters ranging from 160 to 400 nm. Sodium diclofenac was used as a drug model and 95% of the drug was uptake by nanohydrogels. After two hours, the release of diclofenac was 20% higher in the presence of glutathione, reaching 100% of the drug released after 9 hours. The gelatin nanohydrogels obtained show potential features to be employed as a drug delivery system.