June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection
Author Affiliations & Notes
  • Di Huang
    Ophthalmology, The University of Auckland, Auckland, New Zealand
  • Ying-Shan Chen
    Ophthalmology, The University of Auckland, Auckland, New Zealand
  • Ilva D Rupenthal
    Ophthalmology, The University of Auckland, Auckland, New Zealand
  • Footnotes
    Commercial Relationships   Di Huang, None; Ying-Shan Chen, None; Ilva Rupenthal, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4101. doi:
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      Di Huang, Ying-Shan Chen, Ilva D Rupenthal; Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4101.

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

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Abstract

Purpose : Intravitreal injection is the most common and effective administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient drug delivery, especially when aiming to deliver peptides and proteins with short half-lives. This work aimed to improve the vitreous mobility and retinal permeability of intravitreally administered peptides using a combination of nanocarriers and ultrasound (US) in order to achieve a more efficient and prolonged clinical effect.

Methods : Ex vivo bovine eye cups were utilized and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid (HA) coated fluorescein isothiocyanate-labelled connexin43 mimetic peptide (FITC-Cx43 MP) loaded human serum albumin nanoparticles (HSA NPs) were prepared and administered into the ex vivo eye cups followed by continuous US application with a frequency of 1 MHz, an intensity of 0.5 W/cm2, and a duration of 30 s once or repeatedly. After pre-determined time points, fluorescence intensities in the vitreous or the retinal tissues were analyzed. Moreover, histological examination of the retina and sclera/choroid was performed to determine whether the employed US parameters caused any damage to the ocular tissues.

Results : HA coated NPs were successfully formulated with a particle size of 252.70 ± 7.29 nm and a highly negative surface charge of -43.97 ± 0.38 mV, rendering them suitable for intravitreal administration. Compared to passive penetration of NPs, brief US application significantly increased the retinal permeability of NPs (p ≤ 0.05). The effect of US-enhanced permeation was shown to be reproducible with a temporary window of less than 15 min and repeated US application led to a more significant improvement in retinal permeability than single treatment (p ≤ 0.001). Short pulses of US also enhanced the mobility of intravitreally administered NPs through the vitreous with used US conditions not causing any detectable damage to the ocular tissues.

Conclusions : This work showed that US in combination with nanocarriers could be a powerful and safe tool to enhance retinal peptide delivery after intravitreal injection.

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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