Nanodelivery of doxorubicin for age-related macular degeneration

Objective: Polymeric nanoparticles (NPs) containing doxorubicin (DOX) were prepared for the inhibition of hypoxia-induced factor 1 alpha (HIF-1 alpha). Methods: DOX NPs were prepared using both polylactic coglycolic acid (PLGA) and chitosan. PLGA NPs were prepared via nanoprecipitation (NPC) and single and double emulsion diffusion (SE; DE). Chitosan NPs were formulated using ionic gelation (IG), and complex coacervation (CC). Size, polydispersity index (PDI), and zeta potential (ZP) were determined via dynamic light scattering (DLS) (n = 3). The encapsulation efficiency (EE), drug loading capacity (DLC) (n = 3) and in vitro drug release profiles (IVR) at 37 degrees C (n = 4) were analyzed via spectroscopy at 480 nm (lambda(max)). The cytotoxicity of each formulation as well as free DOX solution in ARPE-19 cells was determined via MTT assay after 24 h (n = 3). HIF-1 alpha and VEGF inhibition in ARPE-19 cells were measured via ELISA (n = 3). Results: The results were consistent with the hypothesis; the NP formulations decreased HIF-1 alpha and VEGF-A expression in ARPE-19 cells with reduced cytotoxicity. SE, DE, and CC demonstrated low ZP as well as the most rapid drug release of the tested formulations. FTIR confirmed the presence of DOX on the SE NP surface, indicating instability. Conclusions: SE, DE, and CC destabilized. NPC was the most efficient formulation for the nanodelivery of DOX for AMD.