Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease.
Publication/Presentation Date
2-1-2005
Abstract
PURPOSE: To develop a local drug delivery system that provides therapeutic cyclosporine levels to treat lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
METHODS: Episcleral cyclosporine implants were manufactured with a silicone-based matrix design, and in vitro release rates were determined. Preclinical evaluation included toxicology (clinical examination, serial electroretinography, and histopathology) in normal rabbits and dogs, pharmacokinetics in normal rabbits, and pharmacodynamics in a canine model of aqueous tear deficiency and keratoconjunctivitis sicca.
RESULTS: The cyclosporine implants showed sustained release of drug over time with in vitro assays. Histopathology showed normal ocular tissues in both dogs and rabbits 6 months after implantation. The cyclosporine implant produced lacrimal gland drug levels 1 to 2 log units higher than those reported with a variety of topical cyclosporine formulations and oral administration. The cyclosporine implant was effective in a canine model of keratoconjunctivitis sicca, with all animals able to discontinue topical cyclosporine and maintain normal Schirmer scores over a 6-month follow-up.
CONCLUSIONS: This preclinical evaluation showed that the episcleral cyclosporine implant was safe, delivered potentially therapeutic cyclosporine levels to the lacrimal gland, and showed efficacy in a clinically relevant model of keratoconjunctivitis sicca. The episcleral cyclosporine implant shows promise in reducing the morbidity associated with lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In addition, continuous release of cyclosporine in the subconjunctival space with the episcleral implant was an effective means of delivering drug to the ocular surface and may have potential in treating other ocular inflammatory diseases.
Volume
46
Issue
2
First Page
655
Last Page
662
ISSN
0146-0404
Published In/Presented At
Kim, H., Csaky, K. G., Gilger, B. C., Dunn, J. P., Lee, S. S., Tremblay, M., de Monasterio, F., Tansey, G., Yuan, P., Bungay, P. M., Lutz, R. J., & Robinson, M. R. (2005). Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease. Investigative ophthalmology & visual science, 46(2), 655–662. https://doi.org/10.1167/iovs.04-1076
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
15671296
Department(s)
Administration and Leadership
Document Type
Article