March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Nanostructured Biopolymer Films for Retinal Drug Delivery
Author Affiliations & Notes
  • Kevin D. Lance
    UCSF, San Francisco, California
  • Daniel A. Bernards
    UCSF, San Francisco, California
  • Natalie A. Ciaccio
    UCSF, San Francisco, California
  • Robert B. Bhisitkul
    UCSF, San Francisco, California
  • Tejal A. Desai
    UCSF, San Francisco, California
  • Footnotes
    Commercial Relationships  Kevin D. Lance, Santen, Inc. (F); Daniel A. Bernards, Santen, Inc. (F); Natalie A. Ciaccio, Santen, Inc. (F); Robert B. Bhisitkul, Santen, Inc. (C); Tejal A. Desai, Santen, Inc. (F)
  • Footnotes
    Support  NIH Grant 2 T32 GM 8155-27
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 441. doi:
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      Kevin D. Lance, Daniel A. Bernards, Natalie A. Ciaccio, Robert B. Bhisitkul, Tejal A. Desai; Nanostructured Biopolymer Films for Retinal Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2012;53(14):441.

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

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Purpose: : The goal of this research is to develop a sustained drug delivery device for intraocular release of therapeutics, with a focus on the treatment of age-related macular degeneration (AMD). We investigate the ocular tolerance, structural durability, and functionality of our nanoporous biopolymer devices.

Methods: : We utilized a modular fabrication approach with polycaprolactone (PCL) that combines template-based fabrication to produce nanopores and a polymer mixture to generate a mechanically robust supporting layer. PCL-based devices were characterized in vitro to assess physical degradation and the characteristic release of model therapeutics. Parallel experiments in microporous PCL devices were used to characterize drug payload stability for a model antibody. New Zealand White rabbits were used for our in vivo studies. Structured poly(caprolactone) (PCL) thin films were implanted in rabbit eyes for survival studies and surveillance of ocular tolerability up to 9 months. Histology of enucleated post-mortem eyes was used to evaluate morphologic abnormalities and adverse reactions; scanning electron microscopy was used to examine the durability and stability of extracted thin films. Complete devices loaded with IgG were implanted for a 6 week feasibility study, and vitreous and device samples were analyzed to gauge device performance and payload stability.

Results: : Devices utilizing nanoporous thin films for controlled release exhibit constant rates of release in vitro for greater than 6 months. Model protein drug payloads maintained stability at least 10 weeks. Nanostructured thin films lacked an observable immune response through 9 months of implantation. Structural integrity of implanted films was maintained throughout this time course in vivo. Equivalent films tested in vitro became increasingly fragile after 1 year and had noticeable structural breakdown occurring in excess of 1 year. A short duration in vivo trial with completed devices demonstrated stable activity for the IgG payload over the course of 6 weeks.

Conclusions: : The fabrication procedures we have developed are capable of generating robust nanoporous biopolymer films, and preliminary studies have established several important benchmarks of device function, including sufficient drug loading, controlled release of therapeutic over extended times, materials biocompatibility, and maintenance of drug activity.

Keywords: age-related macular degeneration • vitreoretinal surgery • drug toxicity/drug effects 

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