March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
A Sustained Release, Intra-vitreal Drug Delivery Platform Using An Injectable, Biodegradable, And Biocompatible Reverse Thermal Gel
Author Affiliations & Notes
  • Thomas R. Friberg
    Ophthalmology/UPMC Eye Center, Department of Bioengineering,
    Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Yadong Wang
    Department of Bioengineering,
    Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Veeral Shah
    Ophthalmology/UPMC Eye Center,
    Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Britta Rauck
    Department of Bioengineering,
    Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Carlos Medina
    Ophthalmology/UPMC Eye Center,
    Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Footnotes
    Commercial Relationships  Thomas R. Friberg, PCT/US2011/027233 (P); Yadong Wang, PCT/US2011/027233 (P); Veeral Shah, None; Britta Rauck, None; Carlos Medina, None
  • Footnotes
    Support  Otero Grant, Fox Center for Vision Restoration; National Institutes of Health CORE Grant P30 EY008098; Eye and Ear Foundation of Pittsburgh, PA; Unrestricted Grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5555. doi:
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      Thomas R. Friberg, Yadong Wang, Veeral Shah, Britta Rauck, Carlos Medina; A Sustained Release, Intra-vitreal Drug Delivery Platform Using An Injectable, Biodegradable, And Biocompatible Reverse Thermal Gel. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5555.

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

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Abstract

Purpose: : Sustained release of therapeutic agents into the eye is desirable, theoretically decreasing the treatment burden for patients suffering from eye diseases, and macular degeneration in particular. We investigated the feasibility of using a biodegradable reverse thermal gel (PureSet), which changes from a liquid to a gel when its temperature is increased. This transition occurs near body temperature and can be adjusted, allowing the drug containing liquid to be injected through a 30 gauge needle. The drug gels quickly within the eye. While others have reported related strategies using PolyNPAN polymers, those contain a different backbone and do not easily biodegrade. PureSet gel does not have a carbon backbone, is biodegradable, and injurious chemicals are not used during the loading of the pharmaceutical agents, eliminating the problem of toxic residues. In addition, the gel is transparent.

Methods: : We loaded PureSet gel with by mixing it with 1.25 mg of bevacizumab (Avastin) until a homogenous liquid phase was produced. We tested the biocompatibility of the loaded and unloaded gel in cell culture, using human corneal endothelial and retinal pigment epithelial cell monolayers. Exposure to the gel had no affect on these cells and we went forward with in vivo testing. We injected 0.05 ml of bevacizumab containing gel (1.25 mg) into 4 rabbit eyes, and 0.05 ml of the standard bevacizumab solution (100mg/4ml) into 2 eyes as a control. We sampled anterior chamber fluid by paracentesis in each eye at 1 and 2 weeks, and 1 and 2 months. Using an enzyme-linked immunoassay (ELISA), we measured bevacizumab levels to study the pharmacokinetics.

Results: : At 1 week, the concentration of bevacizumab in both control and gel containing eyes was 3,000 to 10,000 ng/ml. At 28 days, no bevacizumab was detected in controls, but in gel containing eyes, the concentration was 1,000 to 4,000 ng/ml, which is in the therapeutic range. Upon indirect ophthalmoscopy and histopathological study, we found no evidence of inflammation induced by the slow release gel, which could easily be seen in the inferior vitreous as a transparent sphere.

Conclusions: : This reverse thermal gel allows for slow, sustained release of bevacizumab. In addition, more bevacizumab can be loaded into the gel than in a bolus injection because of the controlled release process. Considering the necessity of multiple injections to treat chronic retinal diseases over several years time, complete biodegradability is an advantage, as unwanted debris does not build up within the eye. Furthermore, this strategy allows for a better loading efficiency that when using microspheres, and avoids some of their risks.

Keywords: age-related macular degeneration • vitreous 
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