September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dexamethasone sodium phosphate-loaded biodegradable nanoparticles for treating experimental autoimmune uveitis
Author Affiliations & Notes
  • Qingguo Xu
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Lixia Luo
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jin Yang
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
    Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China
  • Yumin Oh
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Matthew J. Hartsock
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Shiyu Xia
    Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States
  • David G. Emmert
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Charles Eberhart
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • walter J stark
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Elia J Duh
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Justin Hanes
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Qingguo Xu, Johns Hopkins University (P); Lixia Luo, Johns Hopkins University (P); Jin Yang, None; Yumin Oh, None; Matthew Hartsock, None; Shiyu Xia, None; David Emmert, None; Charles Eberhart, None; walter stark, Johns Hopkins University (P); Elia Duh, None; Justin Hanes, Graybug Inc (I), Johns Hopkins University (P)
  • Footnotes
    Support  Raymond Kwok Family Research Fund, the Andreas Dracopoulos Research fund, EBAA/Richard Lindstrom Research Grant 2013
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Qingguo Xu, Lixia Luo, Jin Yang, Yumin Oh, Matthew J. Hartsock, Shiyu Xia, David G. Emmert, Charles Eberhart, walter J stark, Elia J Duh, Justin Hanes; Dexamethasone sodium phosphate-loaded biodegradable nanoparticles for treating experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Autoimmune uveitis, featured by the intraocular inflammation, is a leading cause of visual impairment and blindness. It is challenging to treat the disease, especially in intermediate, posterior- and pan-uveitis that affect the retina and choroid. We have developed biodegradable polymeric nanoparticles (NP) loaded with water-soluble dexamethasone sodium phosphate (DSP), or DSP-NP, to treat experimental autoimmune uveitis (EAU) following subconjunctival (SC) injection.

Methods : DSP-NP were prepared by a nanoprecipitation method, and characterized in terms of particle size, surface charge, particle morphology, drug loading and drug release in vitro. The drug levels in the ocular tissues and blood were determined by measuring the radioactivity of [H3]-labelled DSP following SC injection of DSP-NP in rats. EAU was induced by interphotoreceptor retinoid binding protein (IRBP) in rats. EAU rats were treated at post-immunization day (PID) 8 with a 30 µL SC injection of: (1) DSP-NP (6 mg DSP/mL), (2) DSP free drug (6 mg DSP/mL), (3) PBS. Animals were followed until PID18. Clinical evaluation, slit lamp and fundus imaging, histopathological analysis, electroretinography (ERG), mRNA expression level of inflammatory cytokines (IL17, TNFα, IL2) in retina and iris were performed.

Results : The DSP-NP exhibited a drug loading of 6wt.% and a diameter of 210 nm (Fig1A). DSP-NP sustained the release of DSP in vitro for about 2 weeks (Fig1B). DSP effectively reached the vitreous following the SC injection and sustained DSP levels in the vitreous were maintained for at least 2 weeks (Fig1C). We found the SC injection of DSP-NP significantly reduced EAU inflammation in comparison to DSP and PBS treated groups, evidenced by a significantly reduced clinical disease score, decreased expression of various inflammatory cytokines, and preserved retinal structure and function (Fig1D-G).

Conclusions : By delivering DSP-NP through SC injection, this strategy may provide sufficient intraocular drug levels for prolonged period, reduced drug administration frequency, improved patient compliance and increased therapeutic efficacy to treat autoimmune uveitis. DSP-NP were made from all Generally Regarded As Safe materials, facilitating the future translational use.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Figure1: (A-C) Characterization of DSP-NP; (D-G) Efficacy of treating EAU using SC injection of DSP-NP.

Figure1: (A-C) Characterization of DSP-NP; (D-G) Efficacy of treating EAU using SC injection of DSP-NP.

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