April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Bioerodible Sustained-Release Ocular Implants in Mice Deliver Efficacious Concentrations of CsA
Author Affiliations & Notes
  • L. A. Wheeler
    Biological Sciences, Allergan, Inc, Irvine, California
  • M. R. Robinson
    Biological Sciences, Allergan, Inc, Irvine, California
  • M. Attar
    Biological Sciences, Allergan, Inc, Irvine, California
  • K. F. Siemasko
    Biological Sciences, Allergan, Inc, Irvine, California
  • W. Blanda
    Biological Sciences, Allergan, Inc, Irvine, California
  • S. M. Whitcup
    Biological Sciences, Allergan, Inc, Irvine, California
  • M. E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • Footnotes
    Commercial Relationships  L.A. Wheeler, Allergan, Inc., E; M.R. Robinson, Allergan, Inc., E; M. Attar, Allergan, Inc., E; K.F. Siemasko, Allergan, Inc., E; W. Blanda, Allergan, Inc., E; S.M. Whitcup, Allergan, Inc., E; M.E. Stern, Allergan, Inc., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5962. doi:https://doi.org/
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      L. A. Wheeler, M. R. Robinson, M. Attar, K. F. Siemasko, W. Blanda, S. M. Whitcup, M. E. Stern; Bioerodible Sustained-Release Ocular Implants in Mice Deliver Efficacious Concentrations of CsA. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5962. doi: https://doi.org/.

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

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Abstract

Purpose: : To compare mouse ocular tissue concentrations five days after treatment with Cyclosporin A (CsA) bioerodible sustained-release ocular implants (sub-Tenon’s) or topical CsA.

Methods: : Bioerodible CsA implants with a total drug load of 75 µg and an in vitro release rate of 2 µg/day were surgically positioned in the sub-Tenon’s region of both eyes of BALB/c WT female mice (n=5). Tissel fibrin glue was used to close the incision. CsA 0.05% was administered topically to both eyes as a 5 µL drop three times daily (n=5). Following five days of treatment, implant treated mice were sacrificed. Mice treated topically were sacrificed 16 hours post last topical dose. Conjunctiva, cornea, lacrimal gland, retina, sclera, aqueous humor, blood and superficial cervical lymph nodes were collected, weighed, and CsA levels in these tissues were analyzed by LC-MS/MS. The quantitation range in all tissues was 0.1 to 200 ng.

Results: : BALB/c WT mice receiving CsA implants had detectable levels of CsA in the conjunctiva (10.32 ng/g+/- 1.26), cornea (6.48 ng/g+/-1.84), lacrimal gland (0.075 ng/g+/-0.004), retina (25.32 ng/g+/-7.18), and the sclera (46.19 ng/g+/-13.83). These levels were comparable to CsA levels measured in topically treated mice. Levels of CsA in the aqueous humor, superficial cervical lymph node, and the blood were below the level of quantification in both implant and topically treated mice.

Conclusions: : These results show that implants provide sustained release of CsA that are comparable to CsA levels achieved following topical administration. This study demonstrates the potential of bioerodible implants to deliver an efficacious concentration of CsA to treat ocular inflammatory diseases. Sustained drug levels and improved patient compliance may result in enhanced therapy for ocular inflammatory diseases.

Keywords: conjunctiva • inflammation • cornea: basic science 
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