ABSTRACT
Dexamethasone (DEX) is a synthetic cortisol used for the treatment of different pathological states, thus comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects related to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive target of active pharmaceutical ingredients and the selective internalization into leukemic cells has been demonstrated. Peptide based HG loaded with DEX were formulated via the “solvent-switch” method, using Fmoc-FF homopeptide as building block. Due to the tight interaction of the drug with the peptidic matrix, a significant rigidification of the gel (G’ = 67.9 kPa) was observed. The corresponding injectable NG, obtained for submicronization of the HG in the presence of two stabilizing agents (TWEEN®60 and SPAN®60, 48/52 mol/mol), were found to be stable at least up to 90 days with a mean diameter of around 105 nm. NG does not exhibit hemolytic effect on human serum and is selectively internalized by RS411 leukemic cells, passively target leukemic cells over healthy PBMCs, paving the way for the generation of new diagnostic strategies targeting onco-hematological diseases.