June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Controlled and Extended Release of Bioactive Aflibercept from a Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System
Author Affiliations & Notes
  • Wenqiang Liu
    Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States
  • Bao-Shiang Lee
    Research Resource Center, University of Illinois at Chicago, Chicago, Illinois, United States
  • William F Mieler
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Jennifer J Kang-Mieler
    Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Wenqiang Liu, None; Bao-Shiang Lee, None; William Mieler, None; Jennifer Kang-Mieler, Microsphere-hydrogel ocular drug delivery (P)
  • Footnotes
    Support  NIH EY 013121
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3767. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Wenqiang Liu, Bao-Shiang Lee, William F Mieler, Jennifer J Kang-Mieler; Controlled and Extended Release of Bioactive Aflibercept from a Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3767.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Current therapies for chronic posterior segment diseases often require repeated intravitreal bolus injections of anti-vascular endothelial growth factors. The purpose of this study was to validate a composite microsphere-thermoresponsive hydrogel drug delivery system (DDS) capable of releasing bioactive aflibercept in a controlled and extended manner.

Methods : The composite DDS was developed by suspending aflibercept-loaded poly(lactic-co-glycolic acid) microspheres within a biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate/N-isopropylacrylamide (PEG-PLA-DA/NIPAAm) thermoresponsive hydrogel. Two PEG-PLA-DA concentrations (2mM and 3mM) and two microspheres loading amount (10mg and 20mg) were compared to determine the optimal drug release. The degradation of hydrogel was determined by wet weight changes and normalized to percent degradation. The cytotoxicity from degraded byproducts was investigated by quantifying viability of human umbilical vascular endothelial cells using fluorescent LIVE/DEAD® assay kit. A radioisotope, Iodine-125, was used to label aflibercept and monitor its release from DDS. Finally, a dot blot assay was used to determine the bioactivity of released drug from DDS.

Results : Higher PEG-PLA-DA concentration (3mM) degraded more and faster than the lower concentration (2mM). There was no significant cytotoxicity from degraded DDS byproducts for all investigated time. The amount and rate of aflibercept release can be controlled by both the cross-linker concentration and microspheres load amount. All investigated systems were capable of releasing aflibercept in a controlled manner. The initial burst (release within first 24hr) was 37.35±2.51µg and 74.56±3.14µg (2mM and 3mM hydrogel, each loaded with 10mg and 20mg of microspheres, respectively), followed by a controlled drug release of 0.09µg/day (2mM hydrogel) and 0.19µg/day (3mM hydrogel). A strong binding activity was observed for initial burst samples, which corresponds to a large initial release. The later time point samples also showed bioactivity but lower binding activity, which corresponds to a lower daily release rate.

Conclusions : The results indicate the proposed DDS is safe and can deliver bioactive aflibercept in a controlled manner. The proposed DDS may provide a significant advantage over current bolus injection therapies in the treatment of posterior segment diseases.

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

×
×

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.

×