June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Production and characterization of a sustained release system of dasatinib to prevent proliferative vitreoretinopathy
Author Affiliations & Notes
  • Shigeo Tamiya
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Rajat Chauhan
    BioEngineering, University of Louisville, Louisville, Kentucky, United States
  • Rayeanne Balgemann
    BioEngineering, University of Louisville, Louisville, Kentucky, United States
  • Hidetaka Noma
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
    Ophthalmology, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan
  • Kevin McDonald
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Henry J Kaplan
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky, United States
  • Martin O'Toole
    BioEngineering, University of Louisville, Louisville, Kentucky, United States
  • Footnotes
    Commercial Relationships   Shigeo Tamiya, None; Rajat Chauhan, None; Rayeanne Balgemann, None; Hidetaka Noma, None; Kevin McDonald, None; Henry Kaplan, None; Martin O'Toole, None
  • Footnotes
    Support  DoD BAA Award#W81XWH-15-1-0298; Research to Prevent Blindness Unrestricted Award; KY Lions Eye Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4759. doi:
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      Shigeo Tamiya, Rajat Chauhan, Rayeanne Balgemann, Hidetaka Noma, Kevin McDonald, Henry J Kaplan, Martin O'Toole; Production and characterization of a sustained release system of dasatinib to prevent proliferative vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4759.

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

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Abstract

Purpose : Traction retinal detachment (TRD) associated with proliferative vitreoretinopathy (PVR), which is caused by the formation and contraction of fibrotic scar tissue on the vitreoretinal surface, remains the major complication following surgical correction for retinal detachment and/or ocular trauma. Whilst we have previously demonstrated that dasatinib, a tyrosine kinase inhibitor currently used for the treatment of chronic myeloid leukemia, can prevent TRD in an in vivo model of PVR, multiple intravitreal injections were required. We hypothesized that a sustained release system of dasatinib can prevent TRD with a single injection; the purpose of this project was to produce and characterize a sustained release system of dasatinib in vitro.

Methods : Spray drying method was utilized to produce dasatinib-incorporated poly(lactic-co-glycolic acid) (PLGA) particles (Das-PLGA). Particle size was measured by SEM. Release profile was determined by suspending Das-PLGA in PBS, and measuring dasatinib content daily. The effect of Das-PLGA on PVR-related cell function was determined using the type I collagen contraction assay, in which contraction of a collagen matrix by cultured porcine retinal pigment epithelial (RPE) cells was examined.

Results : Spray drying produced Das-PLGA with relatively narrow size distribution, with the average size being consistently between 1.0-1.4µm. Das-PLGA had an extended release profile with dasatinib being released beyond three weeks. Compared to PLGA control (without dasatinib), Das-PLGA significantly prevented the contraction of a collagen matrix by cultured RPE cells.

Conclusions : Spray drying reliably produced Das-PLGA with a narrow size distribution and an extended dasatinib release profile. Incorporated dasatinib remained functional as demonstrated by the inhibition of PVR-related function of cultured RPE cells.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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