June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Polymer Nanoparticle Drug Delivery System Prevent Systemic Absorption of Bevacizumab After Intravitreal Injection
Author Affiliations & Notes
  • Lingkun Kong
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Jeroen Pollet
    Pediatrics, Baylor College of Medicne, Houston, TX
  • Michael J. Heffernan
    Pediatrics, Baylor College of Medicne, Houston, TX
  • Footnotes
    Commercial Relationships Lingkun Kong, None; Jeroen Pollet, None; Michael J. Heffernan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5029. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Lingkun Kong, Jeroen Pollet, Michael J. Heffernan, ; Polymer Nanoparticle Drug Delivery System Prevent Systemic Absorption of Bevacizumab After Intravitreal Injection . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5029.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: The major concerns for intravitreal injection of anti-VEGF agent for the treatment of retinal diseases are the systemic absorption of the drug into the bloodstream and fast clearance from the vitreous. We developed a new polymer nanoparticle (NP) intravitreal drug delivery system. We hypothesize that this injectable and biodegradable delivery vehicle for anti-VEGF drugs such as bevacizumab can minimize absorption of the drug into the bloodstream and increase the retention of drug in the vitreous space and retinal tissue.

Methods: Bevacizumab was conjugated to the surface of poly (lactic-co-glycolic acid) nanoparticles (PLGA NP), and was injected to the vitreous of adult FVB mice. Blood and vitreous samples were collected before the treatment and at 2 days, 1 week, 2 weeks, and 4 weeks after the treatment to test serum and vitreous bevacizumab levels. Fluorescence imaging was performed with Nile Red-labeled NP-bevacizumab, using an IVIS® Lumina II in vivo imaging system. The tissue distribution and toxicity of the PLGA NP were studied by histology and confocal microscope. Two-tailed student t-test was used for comparing the means of two variables.

Results: Two days after intravitreal injection, serum levels of bevacizumab were 821 ± 176 ng/mL in the free bevacizumab group and 12 ± 1.5 ng/mL in the NP-bevacizumab group. Two weeks after the injection, the serum levels of bevacizumab were 437 ± 137 ng/mL in the free bevacizumab group and undetectable in the NP-bevacizumab group. One week after intravitreal injection, vitreous levels of bevacizumab were similar for the NP-bevacizumab group and the free bevacizumab group (207.8 ± 65.43 ng/mL vs. 184.5 ± 48.20 ng/mL, respectively). At two weeks, vitreous levels of bevacizumab were 55.6 ng/mL in the NP-bevacizumab group and undetectable in the free bevacizumab injection group. The fluorescence intensity persisted in the eye for up to 4 weeks. NP-bevacizumab were distributed in the anterior chamber, vitreous and all layers of retina. No immediate toxicity was found.

Conclusions: The injectable and biodegradable PLGA NP system can potentially serve as intraocular delivery vehicle for anti-VEGF drugs. This study showed that intravitreal injection of PLGA NP conjugated bevacizumab reduced leakage of the drug into systemic blood stream and prolonged the retention of drug in the vitreous.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×