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Transscleral Diffusion of Carboplatin
An In Vitro and In Vivo Study
Amanda E. Simpson, BS;
Jake A. Gilbert, BS;
David E. Rudnick, MS;
Dayle H. Geroski, PhD;
Thomas M. Aaberg, Jr, MD;
Henry F. Edelhauser, PhD
Arch Ophthalmol. 2002;120:1069-1074.
Objectives 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 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 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 µg/mL
in the vitreous at 1 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 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.
From the Department of Ophthalmology, Duke University Medical Center,
Durham, NC (Ms Simpson); Emory Eye Center, Atlanta, Ga (Ms Simpson, Messrs
Gilbert and Rudnick, and Drs Geroski, Aaberg, and Edelhauser); and Associated
Retinal Consultants, Grand Rapids and Royal Oak, Mich (Dr Aaberg). The authors
have no proprietary interest in the products or companies described in this
article.
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