July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Pharmacokinetics of micellar nanoparticle drug delivery for laser-induced choroidal neovascularization as seen on live ocular imaging.
Author Affiliations & Notes
  • Iris N Mollhoff
    Ophthalmology and Vision Science, UC Davis Eye Center, Sacramento, California, United States
  • SUMAN Kalyan MANNA
    Department of Cell Biology and Human Anatomy, UC Davis Eye-Pod Small Animal Ocular Imaging Laboratory, Davis, California, United States
    Ophthalmology and Vision Science, UC Davis Eye Center, Sacramento, California, United States
  • Wenwu Xiao
    Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California, United States
  • Lu Zhang
    Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California, United States
  • Kit Lam
    Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California, United States
  • Robert J Zawadzki
    Department of Cell Biology and Human Anatomy, UC Davis Eye-Pod Small Animal Ocular Imaging Laboratory, Davis, California, United States
    Ophthalmology and Vision Science, UC Davis Eye Center, Sacramento, California, United States
  • Glenn Yiu
    Ophthalmology and Vision Science, UC Davis Eye Center, Sacramento, California, United States
  • Footnotes
    Commercial Relationships   Iris Mollhoff, None; SUMAN MANNA, None; Wenwu Xiao, None; Lu Zhang, None; Kit Lam, LamnoTherapeutics Inc. (E); Robert Zawadzki, None; Glenn Yiu, Alcon (F), Alimera (C), Allergan (C), Carl Zeiss Meditec (C), Clearside (F), Iridex (C)
  • Footnotes
    Support  NIH K08 EY026101, E.Matilda Ziegler Foundation for the Blind, Barr Foundation for Retinal Research, the California National Primate Research Center, and the CITRIS/Banatao Institute, NIH grants CA198880, EY026556, EY012576 (NEI Core Grant).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6395. doi:
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      Iris N Mollhoff, SUMAN Kalyan MANNA, Wenwu Xiao, Lu Zhang, Kit Lam, Robert J Zawadzki, Glenn Yiu; Pharmacokinetics of micellar nanoparticle drug delivery for laser-induced choroidal neovascularization as seen on live ocular imaging.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6395.

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

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Abstract

Purpose : Intravitreal anti-vascular endothelial growth factor (anti-VEGF) pharmacotherapy is effective for treatment of neovascular age-related macular degeneration (nAMD) and other forms of choroidal neovascularization (CNV), but these injections are invasive, transient, and lack specificity. Micellar nanoparticles (NPs) given intravenously, and optically-triggered in the eye, holds the promise for targeted drug delivery of anti-angiogenesis agents. Here, we explore the ocular pharmacokinetics of intravenous NPs in a mouse model of laser-induced CNV using in vivo ocular imaging.

Methods : Formulations of (1) free rhodamine/NP mixtures, (2) rhodamine-encapsulated NPs, and (3) rhodamine-conjugated NPs ranging in size from 15nm to 21nm were given by tail vein injections in wild-type mice 1 week after laser injury for CNV induction. CNV size and activity were assessed using fluorescein angiography (FA) and optical coherence tomography angiography (OCT-A). Fluorescence scanning-laser ophthalmoscopy (SLO) imaging was used to measure fluorescence intensity and spectra within the CNV lesion, uninjured retina-choroid, and major retinal vessels at time points up to 6 hours.

Results : Free rhodamine/NP mixture showed rapid distribution and removal from CNV and retinal vessels within minutes, but persisted in the retina-choroid up to 6 hours. Rhodamine-encapsulated NPs also showed a similar distribution, but greater retention of rhodamine within CNV lesions up to 1 hour. Rhodamine-conjugated NPs rapidly entered retinal vessels within minutes and maximally-accumulated in CNV lesions at 1 hour, with persistence of fluorescence within CNV lesions and reitnal vessels beyond 6 hours.

Conclusions : The ocular pharmacokinetics of intravenous micellar nanoparticles in CNV lesions can be visualized using in vivo SLO imaging. Compared with free rhodamine, rhodamine-encapsulated NPs demonstrate improved retention in CNV tissues, while rhodamine-conjugated NPs show greatest retention within CNV tissues and retinal vasculature.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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