Harnessing the targeting potential of hyaluronic acid for augmented anticancer activity and safety of duvelisib-loaded nanoparticles in hematological malignancies

Duvelisib (DUV) is effective against numerous hematological malignancies; however, it suffers from numerous setbacks like poor aqueous solubility, low cellular uptake and adverse effects. Hyaluronic acid is an excellent ligand for CD44 receptors that are overexpressed on cancer cell surfaces. Thus, for the targeted delivery of DUV in hematological malignancies, we have fabricated hyaluronic acid-coated polylactide-co-glycolide nanoparticles (DUV-P/CH/HA-NPs) through electrostatic interactions. DUV-P/CH/HA-NPs exhibited optimum characteristics such as mean particle size of 183.63 f 0.23 nm, polydispersity index of 0.261 f 0.02 and drug loading capacity of 5.75 f 0.05 %. An in-vitro release study demonstrated sustained release behavior of DUV-P/CH/HA-NPs (77.65 f 2.89 % release in 48 h). The flow cytometry experiments revealed 1.62-fold and 1.50-fold enhanced uptake of DUV-P/CH/HA-NPs compared to non-coated nanoparticles in MOLT-4 and HH cells, respectively. The DUV-P/CH/HA-NPs showed higher cytotoxicity, arrested the cell cycle in G0/G1 phase and showed increased apoptosis compared to non-coated nanoparticles and free DUV. An in-vivo pharmacokinetic study revealed 2.9fold and 3.6-fold enhancement in AUC0-tand MRT with the DUV-P/CH/HA-NPs compared to free DUV. Further, toxicity evaluation and hemolysis assessment of DUV-P/CH/HA-NPs indicated good safety for intravenous administration. Conclusively, DUV-P/CH/HA-NPs are an excellent option for selectively targeting hematological malignant cells.