Transscleral permeability and intraocular concentrations of cisplatin from a collagen matrix

This study determined the in vitro permeability of cisplatin through isolated human sclera as delivered by a collagen matrix vehicle. Short-term and long-term intraocular levels of cisplatin were also measured in the rabbit eye after a subconjunctival injection. Cisplatin in either a collagen matrix vehicle or a control balanced salt solution (BSS) vehicle was applied to human sclera mounted in a specially designed in vitro perfusion chamber. The amount of cisplatin that diffused across the sclera was measured in hourly samples for 24 h using atomic absorption spectrometry. In vivo studies were also performed in Dutch Belted rabbits given subconjunctival injections of cisplatin in collagen matrix or in BSS. Eyes were enucleated at 1.5 h and 2 weeks after injection, frozen, and dissected to determine the intraocular cisplatin concentrations. Cisplatin had a peak in vitro scleral permeability constant of 8.3±1.2×10 −6 and 20.1±1.8×10 −6 cm/s, delivered in collagen matrix and in BSS, respectively (mean±S.D.). At the end of the in vitro experiments, 35.9±4.6% of the cisplatin remained in the collagen matrix, while 0.8±0.2% remained in the BSS vehicle. Subconjunctival injection of cisplatin in the collagen matrix vehicle achieved 3.3±0.1 μg/ml in the vitreous humor at 1.5 h and 0.1±0.1 μg/ml at 2 weeks. This vehicle also achieved a cisplatin concentration of 73.5±23.9 μg/mg in the choroid and retina at 1.5 h and 3.2±1.3 μg/mg at 2 weeks. Compared to BSS, the collagen matrix vehicle provided a more controlled release of cisplatin, and after subconjunctival injection into rabbits, attained higher drug levels in several ocular tissues.