July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Nanodelivery of Doxorubicin for Age-Related Macular Degeneration
Author Affiliations & Notes
  • Shannon J Kelly
    Pharmaceutical Sciences, University of South Florida, Tampa, Florida, United States
  • Kathleen Halasz
    Pharmaceutical Sciences, University of South Florida, Tampa, Florida, United States
  • Vijaykumar Sutariya
    Pharmaceutical Sciences, University of South Florida, Tampa, Florida, United States
  • Footnotes
    Commercial Relationships   Shannon Kelly, None; Kathleen Halasz, None; Vijaykumar Sutariya, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1458. doi:
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    • Get Citation

      Shannon J Kelly, Kathleen Halasz, Vijaykumar Sutariya; Nanodelivery of Doxorubicin for Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1458.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Hypoxia-induced factor 1α (HIF-1α) is responsible for the upregulation of many angiogenic factors, including vascular endothelial growth factor (VEGF). Doxorubicin (DOX) blocks HIF-1α from binding to DNA thereby preventing the downstream upregulation of these factors; however, DOX is highly toxic. This experimental study demonstrates that by encapsulating DOX in a polymeric nanoparticle, the delivery will be sustained and its toxicity will be reduced without limiting efficacy.

Methods : DOX nanoparticles (NPs) and blank NPs were prepared via these methods and characterized to determine the best formulation for our purpose: nanoprecipitation (NPC), single and double emulsion diffusion (SE; DE), and ionic gelation (IG). Size, polydispersity index (PDI), and zeta potential (ZP) were determined via dynamic light scattering (DLS) (n=3). The encapsulation efficiency (EE) (n=3) and in vitro release (IVR) of these NPs at 37°C (n=4) was analyzed via spectroscopy at 480nm. The cytotoxicity of each formulation and free DOX in solution to human retinal pigment epithelial (ARPE-19) cells was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assay after 24 hours (n=3). HIF-1α and VEGF inhibition in ARPE-19 cells were measured via enzyme-linked immunosorbent assay (ELISA) (n=3).

Results : SE and DE NPs possessed a ZP with a lower magnitude than 25mV (-3.83±0.0802, 0.0623±0.034, and 2.61±0.154 mV, respectively), indicative of instability. FT-IR results confirm the presence of DOX on the surface of SE NPs. The drug release of SE and DE also demonstrate a more rapid burst release within the first 8 hours than IG and NPC, supporting the destabilization (Fig. 1). Each NP formulation demonstrated a sustained release of drug and inhibited HIF-1α and VEGF-A expression in ARPE-19 cells with low cytotoxicity after 24 hours. NPC had the highest EE (90.35 ± 0.1513%).

Conclusions : The results were consistent with the hypothesis; the NP formulations decreased HIF-1α and VEGF-A expression in ARPE-19 cells with reduced cytotoxicity. NPC was the most NPC NPs were the most efficient NP formulation for the nanodelivery of DOX for AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1. Each NP formulation demonstrated a sustained in vitro drug release.

Figure 1. Each NP formulation demonstrated a sustained in vitro drug release.

 

Table 1. Characteristics of each NP formulation

Table 1. Characteristics of each NP formulation

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