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. Methods: 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. Results: In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 ± 2.3 ϫ 10 −6 cm/s; carboplatin in BSS, 27.0 ± 1.7 ϫ 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 µg/mL in the vitreous at 1 1 ⁄2 hours and 0.03±0.06 µg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59±177.84 µg/mg in the choroid and retina at 1 1 ⁄2 hours and 3.38±1.97 µg/mg in the choroid and retina at 2 weeks. (Data are given as mean±SEM.) Conclusion: Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks. Clinical Relevance: 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.
Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mm Hg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mm Hg a 10-fold decrease was observed compared with that at 0 mm Hg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.
Subconjunctival delivery of carboplatin in fibrin sealant or BSS does not have a toxic effect on retinal function or structure in a non-tumor-bearing rabbit model at the doses used in this study at 3 weeks' follow-up.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.