Nanodelivery of doxorubicin for age-related macular degeneration

Abstract

Objective: Polymeric nanoparticles (NPs) containing doxorubicin (DOX) were prepared for the inhibition of hypoxia-induced factor 1α (HIF-1α).

Significance: HIF-1α is responsible for the upregulation of several angiogenic factors, including vascular endothelial growth factor (VEGF). DOX inhibits HIF-1α but is highly toxic. By encapsulating DOX in NPs, drug delivery will be sustained and toxicity will be reduced without limiting efficacy.

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 °C (n = 4) were analyzed via spectroscopy at 480 nm (λ_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-1α 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-1α 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.

Keywords:

• Age-related macular degeneration
• hypoxia-induced factors
• doxorubicin
• nanoparticles; vascular endothelial growth factor

Acknowledgments

Special thanks to Ms. Amanda Garces from the USF Lisa Muma Weitz Laboratory for Advanced Microscopy & Cell Imaging for her training and use of the scanning electron microscope. Mr. Gaurav Verma and Dr. Lukasz Wojtas from the USF X-ray Facility and Solid State Characterization Core Lab must also be thanked for their assistance and training using the Fourier transform infrared spectroscope. Thank you to all of the volunteers in Dr. Sutariya’s lab for their support and assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.