A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy

Abstract

The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous.

The mean survival times of animals in the control and placebo groups were statistically equivalent (21 ± 4 days vs 18 ± 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 ± 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 ± 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.

Key Words:

• corneal transplant (keratoplasty)
• transplant rejection
• cyclosporine
• degradable implant
• immunosuppression
• local drug delivery