This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (21)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Ophthalmology, Other  • Alert me on articles by topic

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.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Subconjunctival Topotecan in Fibrin Sealant in the Treatment of Transgenic Murine Retinoblastoma
Tsui et al.
IOVS 2008;49:490-496.
ABSTRACT | FULL TEXT  

Topotecan Vitreous Levels after Periocular or Intravenous Delivery in Rabbits: An Alternative for Retinoblastoma Chemotherapy
Carcaboso et al.
IOVS 2007;48:3761-3767.
ABSTRACT | FULL TEXT  

Pharmacokinetics of Intraocular Drug Delivery by Periocular Injections Using Ocular Fluorophotometry
Ghate et al.
IOVS 2007;48:2230-2237.
ABSTRACT | FULL TEXT  

Bovine and Porcine Transscleral Solute Transport: Influence of Lipophilicity and the Choroid-Bruch's Layer.
Cheruvu and Kompella
IOVS 2006;47:4513-4522.
ABSTRACT | FULL TEXT  

Topotecan Combination Chemotherapy in Two New Rodent Models of Retinoblastoma
Laurie et al.
Clin. Cancer Res. 2005;11:7569-7578.
ABSTRACT | FULL TEXT  

CAI Is a Potent Inhibitor of Neovascularization and Imparts Neuroprotection in a Mouse Model of Ischemic Retinopathy
Franklin et al.
IOVS 2004;45:3756-3766.
ABSTRACT | FULL TEXT  

Subconjunctival Nano- and Microparticles Sustain Retinal Delivery of Budesonide, a Corticosteroid Capable of Inhibiting VEGF Expression
Kompella et al.
IOVS 2003;44:1192-1201.
ABSTRACT | FULL TEXT