Transscleral diffusion of carboplatin: an in vitro and in vivo study

To compare the in vitro scleral permeability of carboplatin using either a fibrin sealant or a balanced salt solution (BSS) vehicle and to measure in vivo ocular tissue levels following subconjunctival injection of carboplatin in fibrin sealant or BSS.

The permeability of carboplatin in fibrin sealant or BSS through human eye bank sclera was tested using an in vitro perfusion apparatus. Levels of carboplatin permeating the sclera were measured every hour for 24 hours using atomic absorption spectrometry. In vivo studies were performed in Dutch Belted rabbits injected subconjunctivally with carboplatin in either fibrin sealant or BSS; eyes were enucleated at 1(1/2) hours, 48 hours, and 2 weeks after injection, and levels of carboplatin were measured in various tissues.

In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 +/- 2.3 x 10(-6) cm/s; carboplatin in BSS, 27.0 +/- 1.7 x 10(-6) cm/s. After 24 hours, 33.2% +/- 1.8% of the carboplatin was retained in the fibrin sealant, while 5.5% +/- 1.0% was retained in the BSS. In vivo subconjunctival injection of carboplatin in fibrin sealant vehicle achieved 11.83 +/- 5.16 microg/mL in the vitreous at 1(1/2) hours and 0.03 +/- 0.06 microg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59 +/- 177.84 microg/mg in the choroid and retina at 1(1/2) hours and 3.38 +/- 1.97 microg/mg in the choroid and retina at 2 weeks. (Data are given as mean +/- SEM.)

Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks.

This study reports the use of fibrin sealant as a subconjunctival delivery vehicle for carboplatin, and quantifies ocular drug levels achieved in an animal model.