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Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification
Gervais, Kristen J

2017, Master of Science, Ohio State University, Comparative and Veterinary Medicine.
Purpose: To utilize a thermosensitive hydrogel (thermogel) polymer to achieve sustained release of cyclosporine A (CsA) for targeted destruction of lens epithelial cells (LEC) and reduction of posterior capsule opacification (PCO) after cataract surgery. Part I of the study evaluated the drug delivery system in an ex vivo canine model of PCO, while Part II evaluated intraocular delivery in an in vivo rabbit model. Methods. A PLGA-PEG-PLGA thermogel polymer was formulated to release CsA ([300µg/mL]) or vehicle (ethanol). PART I: Extracapsular cataract extraction and intraocular lens (IOL) placement were performed in 24 canine cadaver globes. Lens capsule explants with residual LEC were treated with 200µL of CsA-eluting (n=12) or vehicle-eluting (n=12) thermogel and maintained in culture. Posterior capsule coverage by LEC was graded following 7 (n=8), 14 (n=6), or 28 (n=10) days of treatment. Following histology, LEC were manually quantified via light microscopy from capsules treated for 28-days. CsA concentration in culture media was quantified by tandem liquid chromatography-mass spectrometry (LC-MS/MS) at each time point. Differences in percent posterior capsule coverage and LEC counts were analyzed by the student’s t-test with Welch’s correction. PART II: Phacoemulsification cataract surgery and IOL placement were performed in 10 adult rabbits (20 eyes). Ten left eyes served as negative controls and were treated with viscoelastic material only. Five right eyes were treated with 200µL CsA-eluting thermogel polymer, and five right eyes were treated with vehicle-eluting thermogel polymer. Clinical ophthalmic examination parameters and PCO grading were performed daily for 6 days post-operatively, and then weekly until the termination of the study at 49 days. Aqueous humor samples were analyzed for CsA concentration at day 6 post-operatively. Following euthanasia, globes were collected and analyzed histologically for degree of PCO formation and any evidence of ocular toxicity. Clinical examination parameters were compared between treatment groups using the Wilcoxon signed rank or Wilcoxon rank sum test. Results. PART I: Posterior capsule coverage by LEC was significantly reduced in CsA-thermogel treated capsules compared to vehicle-treated capsules. Histologic LEC counts were significantly lower in CsA-thermogel treated capsules. Cumulative CsA release from the thermogel was greater than 10µg/mL over a minimum of 7 days. PART II: No significant differences in clinical PCO scores were identified when comparing treatment with CsA-eluting thermogel to vehicle-eluting thermogel. The rate of onset and severity of PCO formation were significantly decreased in thermogel-treated eyes (CsA- and thermogel-treated data combined) compared to non-thermogel-treated eyes up to 4 weeks post-operatively. At the conclusion of the study, no significant differences in PCO formation were found clinically or histologically between treatment groups. The mean aqueous humor CsA level at day 6 post-operatively was 3.2pg/mL. No direct toxic effects of the thermogel polymer or CsA were documented in any eyes. Conclusions. Use of a CsA-eluting thermogel polymer may be a viable pharmacologic method for inducing targeted LEC death and reducing PCO formation. Intraocular administration of the drug delivery system is feasible and does not result in ocular toxicity.
Heather Chandler (Advisor)
91 p.

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Gervais, K. (2017). Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Gervais, Kristen. "Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification." Electronic Thesis or Dissertation. Ohio State University, 2017. OhioLINK Electronic Theses and Dissertations Center. 15 Dec 2017.

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Gervais, Kristen "Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification." Electronic Thesis or Dissertation. Ohio State University, 2017. https://etd.ohiolink.edu/

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