Efficacy of subconjunctival cyclosporin-containing microspheres on keratoplasty rejection in the rabbit

• Published in: Graefe's archive for clinical and experimental ophthalmology 1999-10, Vol.237 (10), p.840-847
• Main Authors: DE ROJAS SILVA, M. V, RODRIGUEZ-ARES, M. T, SANCHEZ-SALORIO, M, LAMAS DIAZ, M. J, CUEVAS ALVAREZ, J, VILA JATO, J. L, CAPEANS TOME, C
• Format: Article
• Language: English
• Subjects: Animals; Aqueous Humor - metabolism; Biocompatible Materials; Biological and medical sciences; Conjunctiva; Cornea - metabolism; Cornea - pathology; Corneal Transplantation - pathology; Cyclosporine - administration & dosage; Cyclosporine - pharmacokinetics; Disease Models, Animal; Drug Delivery Systems; Graft Rejection - metabolism; Graft Rejection - pathology; Graft Rejection - prevention & control; Graft Survival; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Injections; Lactic Acid; Medical sciences; Microspheres; Ophthalmology; Pharmacology. Drug treatments; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rabbits; Radioimmunoassay; Treatment Outcome
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s004170050321

The purpose of this study was to evaluate microspheres of PLGA containing cyclosporin (CsA) as a subconjunctival drug delivery system and to test their efficacy in the prevention of corneal allograft rejection in the rabbit. Rabbits were injected subconjunctivally with a solution of CsA (CsA-AR) (20 animals) or a microsphere suspension of CsA (CsA-MP) (20 animals), with equivalent drug concentrations (15 mg/ml). The concentration of CsA in the aqueous, cornea and blood was measured by radioimmunoassay at different times thereafter. In other rabbits, 40 allogeneic grafts were performed. Animals were divided into four groups that received the following subconjunctival treatments: group 1: AR solution (solvents of CsA-AR solution); group 2: CsA-AR solution; group 3: MP suspension (empty microspheres); group 4: CsA-MP suspension. Mean corneal levels of CsA were 1174+/-830, 918+/-179, 972+/-580, 268+/-182 and 243+/-162 ng/ml at 12, 24 and 48 h and 7 and 14 days after the injection of CsA-AR. For the CsA-MP suspension, corneal concentrations were 1195+/-321, 234+/-147 and 88+/-77 ng/ml at 12, 24 and 48 h but subsequently dropped to undetectable levels. Blood and aqueous levels were undetectable. Treatment with CsA significantly improved the survival time and survival rate of grafts in the CsA-treated groups (2, 4) over grafts in non-CsA-treated groups (1, 3). There was no significant difference in the graft survival curve between groups 2 and 4. CsA-containing microspheres might be a promising formulation in the prevention of corneal graft rejection. Since the levels of CsA in blood were undetectable, this treatment might avoid the problems associated with systemic side effects.