June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Pharmacokinetics and Clearance of Molecules after Microneedle Injection into the Suprachoroidal Space
Author Affiliations & Notes
  • Bryce Chiang
    Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA
  • Mark R Prausnitz
    Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA
    School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA
  • Footnotes
    Commercial Relationships Bryce Chiang, None; Mark Prausnitz, Clearside Biomedical (C), Clearside Biomedical (F), Clearside Biomedical (P), Clearside Biomedical (R), Clearside Biomedical (S)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5727. doi:
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      Bryce Chiang, Mark R Prausnitz; Pharmacokinetics and Clearance of Molecules after Microneedle Injection into the Suprachoroidal Space. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5727.

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

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Abstract
 
Purpose
 

Microneedle injection into the suprachoroidal space (SCS) enables the highly targeted delivery of molecules to the chorioretina for the treatment of posterior segment diseases. Previous studies have demonstrated significantly faster molecule clearance from the SCS than from the vitreous (i.e., hours vs. weeks). We tested the hypothesis that fluid carrier formulations containing carboxymethyl cellulose (CMC) or Discovisc result in different clearance times from the SCS, and that molecules dissolved in these fluid carriers have longer residence time in the SCS.

 
Methods
 

Fifty microliter microneedle injections were made 3-4 mm posterior to the limbus of albino New Zealand White rabbit eyes. The injectate contained 0.25% (w/v) fluorescein sodium dissolved in (a) HBSS only, (b) 5% (w/v) CMC in HBSS, or (c) Discovisc. Noninvasive ultrasound biomicroscopy (U/S) and fluorescence wide-field fundus imaging were performed pre- and post- injection.

 
Results
 

We wanted to determine the clearance times of the different fluid carriers from the SCS. U/S was used to find the maximal SCS thickness for the three tested fluid carriers (Figure 1). After fitting the data to 2nd order exponential equations, the clearance time constant for the fluid carriers was found to be 1.8 h for HBSS, 167 h for CMC, and 4.7 h for Discovisc.<br /> <br /> Next, we wanted to find the residence time of molecules dissolved in HBSS only or CMC using fluorescence fundus imaging. Though the CMC was visible in the SCS for 3 wk, fluorescein mixed in the CMC was cleared by 4 days (Figure 2, top row). Fluorescein in HBSS was not visible 5 - 12 h post-injection (Figure 2, bottom row). The spreading area within the SCS for HBSS was greater than for CMC.

 
Conclusions
 

The fluid carrier used to perform a microneedle injection into the SCS plays a key role in the spreading pattern and clearance from the SCS. The residence time of molecules in the SCS can be extended with fluid carrier formulations. Additional fluid carriers that cover the entire SCS and prolong residence time of molecules within the SCS are under study.  

 
Maximal SCS thickness over time for HBSS only (red), CMC (blue) and Discovisc (yellow).
 
Maximal SCS thickness over time for HBSS only (red), CMC (blue) and Discovisc (yellow).
 
 
Fluorescence fundus imaging pre- and post- microneedle injection of fluorescein in CMC (top) or HBSS only (bottom).
 
Fluorescence fundus imaging pre- and post- microneedle injection of fluorescein in CMC (top) or HBSS only (bottom).

 
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