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

Autor: de Rojas Silva, Maria Victoria, Rodríguez-Ares, Maria Teresa, Sánchez-Salorio, Manuel, Lamas Díaz, Maria Jesús, Cuevas Alvarez, Juan, Vila Jato, José Luis, Capeans Tomé, Carmela
Zdroj: Graefe's Archive of Clinical & Experimental Ophthalmology; Sep1999, Vol. 237 Issue 10, p840-847, 8p
Abstrakt: · Background: 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. · Methods: 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. · Results: 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. · Conclusion: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index