Prolongation of corneal allograft survival with liposome-encapsulated cyclosporine in the rat eye

Ophthalmology. 1993 Jun;100(6):890-6. doi: 10.1016/s0161-6420(93)31558-7.

Abstract

Purpose: To study the effects of different formulations of topical cyclosporine (Cyclosporin A [CsA]) on corneal allograft rejection in a rat model.

Methods: Female Lewis rats received penetrating keratoplasties from female Wistar-Furth donors. A total of 78 allogeneic grafts were performed. An additional 15 syngeneic grafts (Lewis) were used as technical controls. Two CsA preparations with equivalent drug concentrations (2.1 mg/ml) were applied as drops: CsA encapsulated in large unilamellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). Allogeneic grafts were randomly assigned to receive CsA-LIP or CsA-DR beginning on the day of surgery five times daily for 10 days. Animals without any treatment or receiving empty liposomes (EM-LIP) were used as treatment controls. Grafts were graded three times weekly and a rejection index was generated based on graft clarity, neovascularization, and vessel size.

Results: All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 days, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or EM-LIP treatment groups. The mean survival time of rejected grafts in animals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a significant difference in the mean survival time between the CsA-LIP treatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P < or = 0.05). The Kaplan-Meier survival curve of the CsA-LIP treatment group was significantly different from the other experimental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR group, and 36% in the EM-LIP group.

Conclusion: Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cornea / drug effects*
  • Cornea / pathology
  • Cornea / surgery
  • Cyclosporine / administration & dosage
  • Cyclosporine / blood
  • Cyclosporine / therapeutic use*
  • Drug Carriers
  • Female
  • Graft Survival / drug effects*
  • Keratoplasty, Penetrating*
  • Liposomes
  • Ophthalmic Solutions
  • Rats
  • Rats, Inbred Lew
  • Rats, Inbred WF
  • Transplantation, Homologous

Substances

  • Drug Carriers
  • Liposomes
  • Ophthalmic Solutions
  • Cyclosporine