June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Nanoparticle-medicated delivery of hydrophobic compounds to retinal microvascular endothelial cells
Author Affiliations & Notes
  • Wenbo Zhang
    Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX
    Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX
  • Shuang Zhu
    Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX
  • Shariq Ali
    Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX
  • Alexandra N. Martirossian
    Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX
  • Xiaobing Hu
    Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX
  • Sanaalarab Al-Enazy
    Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX
  • Norah Albekairi
    Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX
  • Massoud Motamedi
    Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX
    Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX
  • Erik Rytting
    Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX
    Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX
  • Footnotes
    Commercial Relationships Wenbo Zhang, None; Shuang Zhu, None; Shariq Ali, None; Alexandra Martirossian, None; Xiaobing Hu, None; Sanaalarab Al-Enazy, None; Norah Albekairi, None; Massoud Motamedi, None; Erik Rytting, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4160. doi:https://doi.org/
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      Wenbo Zhang, Shuang Zhu, Shariq Ali, Alexandra N. Martirossian, Xiaobing Hu, Sanaalarab Al-Enazy, Norah Albekairi, Massoud Motamedi, Erik Rytting; Nanoparticle-medicated delivery of hydrophobic compounds to retinal microvascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4160. doi: https://doi.org/.

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

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Abstract

Purpose: Ischemic retinopathy (IR), including diabetic retinopathy and retinopathy of prematurity, is the leading cause of blindness in persons under 60 years of age in the United States. A major cause of irreversible vision loss in IR is the presence of abnormal retinal neovascurization resulting from pathological angiogenesis. While intravitreally injected large size proteins such as anti-VEGF antibodies can stay in vitreous for long period and effectively block neovascularization, delivery of small anti-angiogenic compounds is challenged by poor drug solubility and rapid ocular elimination. Nanoparticle-based drug delivery involves the encapsulation or incorporation of drugs into microparticles with size and shape at the nanometer scale. It has many advantages over traditional therapeutic methods, such as improved drug efficacy, increased drug solubility and stability, prolonged drug bioavailability, and reduced nonspecific toxicity. This study is to determine whether biocompatible nanoparticles comprised of the FDA-approved biodegradable polymer PLGA (poly(lactic-co-glycolic acid)) or PLA (poly(lactic acid)) can be used to effectively deliver hydrophobic compounds into retinal microvascular endothelial cells (RMECs).

Methods: PLGA and PLA based nanoparticles were prepared by a modified solvent displacement method. Nanoparticles were either loaded with coumarin-6, a fluorescent hydrophobic dye, to visualize and track nanoparticles; or loaded with Pazopanib, a FDA-approved angiogenic inhibitor, to test whether this approach can inhibit the angiogenic ability of RMECs.

Results: PLGA and PLA nanoparticles generated in these studies were negative changed, quite uniform in size, shape and mass distribution, and had diameter ranging from 48 to 144 nm depending on the component of the polymers. They were rapidly uptaken by RMECs within 5 minutes after cells were incubated with the particles. PLGA and the PLA nanoparticles loaded with pazopanib significantly blocked the angiogenic ability of RMECs, such as cell proliferation and migration.

Conclusions: These results indicate that PLGA and PLA nanoparticles can effectively deliver small molecular weight water-insoluble compounds into RMECs and therefore serve as a potential vehicle to deliver anti-angiogenic drug to treat retinal neovascularization.

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