September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
An Injectable, Biodegradable, And Biocompatible Reverse Thermal Gel Designed for Controlled, Intra-vitreal Drug Delivery
Author Affiliations & Notes
  • yadong wang
    university of pittsburgh, Pittsburgh, Pennsylvania, United States
  • Thomas R Friberg
    university of pittsburgh, Pittsburgh, Pennsylvania, United States
  • Mantosh Sinha
    university of pittsburgh, Pittsburgh, Pennsylvania, United States
  • Hassan Awada
    university of pittsburgh, Pittsburgh, Pennsylvania, United States
  • Xiaochu Ding
    university of pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   yadong wang, None; Thomas Friberg, None; Mantosh Sinha, None; Hassan Awada, None; Xiaochu Ding, None
  • Footnotes
    Support  University startup fund
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      yadong wang, Thomas R Friberg, Mantosh Sinha, Hassan Awada, Xiaochu Ding; An Injectable, Biodegradable, And Biocompatible Reverse Thermal Gel Designed for Controlled, Intra-vitreal Drug Delivery. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Sustained release of therapeutic agents into the eye is a highly desirable goal, theoretically decreasing the treatment burden for patients suffering from ophthalmic diseases, and macular degeneration in particular. We have previously designed a biodegradable reverse thermal gel, ESHU, which changes from a liquid to a gel when temperature increases to near body temperature. The drug containing liquid to be easily injected through a 30 G needle. The drug gels quickly within the eye. While others have reported on using reverse thermal gels, those don’t biodegrade. The advantage of ESHU was good biocompatibility and sustained release of bevacizumab (Avastin) up to 3 months in the eye. The limitation of ESHU is the unexpected slow degradation in the eye (approximately 10% at 3 months). Thus we designed a second generation gel, EPSHU, whcih kept the ESHU’s advantages but degraded faster. .

Methods : We loaded EPSHU gel with bevacizumab and tested the release of the drug in 1% hyaluronic acid solution at 37C. Using an enzyme-linked immunosorbant assay (ELISA), we measured bevacizumab levels to study the release profile. We tested the biocompatibility of the unloaded gel in a BALB/cJ mouse subcutaneous model. We have an ongoing tests on the biocompatibility and biodegradation of the gel in rabbit eyes. The gel was injected via 30 G needle in the left eyes of New Zealand white rabbits (n=4).

Results : The gel releases bevacizumab in nearly linear fashion in vitro. At 30 days, approximately 70% of the drug is released. Subcutaneous implantation in mice revealed good biocompatibility and faster gel degradation than our 1st generation gel ESHU. Indirect ophthalmoscopy found no evidence of inflammation induced by the gel. The gel could easily be seen in the inferior vitreous as a near spherical structure and gradually degrade, losing approximately 30-40% of its volume at 45 days.

Conclusions : EPSHU gel is biodegrdable and allows for sustained release of bevacizumab. Furthermore, this strategy allows for a higher loading efficiency than when using microspheres, and avoids some of their risks.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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