Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic\nlupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented\nadverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the\nsustained delivery of dexamethasone were designed to increase both bioavailability and duration of\nthe administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting\nof water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD) moieties adds\nhydrophobic drug-complexing sites. Polyamidoamines (PAAs) are biocompatible and biodegradable\npolymers apt to create CD moieties in hydrogels. In this work, Ã?² or Ã?³-CD/PAA nanogels have been\ndeveloped. In vitro studies showed that a pretreatment for 24ââ?¬â??48 h with dexamethasone-loaded,\nÃ?²-CD/PAA nanogel (nanodexa) inhibits adhesion of Jurkat cells to human umbilical vein endothelial\ncells (HUVEC) in conditions mimicking inflammation. This inhibitory effect was faster and higher\nthan that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression\ninduced by PMA+A23187 in Jurkat cells after 24ââ?¬â??48 h incubation in the 10âË?â??8ââ?¬â??10âË?â??5 M concentration\nrange, while dexamethasone was effective only at 10âË?â??5 M after 48 h treatment. Hence, the novel\nnanogel-dexamethasone formulation combines faster action with lower doses, suggesting the\npotential for being more manageable than the free drug, reducing its adverse side effects.
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