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 x 10(-6) and 20.1+/-1.8 x 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 microg/ml in the vitreous humor at 1.5 h and 0.1+/-0.1 microg/ml at 2 weeks. This vehicle also achieved a cisplatin concentration of 73.5+/-23.9 microg/mg in the choroid and retina at 1.5 h and 3.2+/-1.3 microg/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.
Gilbert
Jake A
JA
Emory Eye Center, Suite B2600, 1365B Clifton Road NE, Atlanta, GA 30322, USA.
Simpson
Amanda E
AE
Rudnick
David E
DE
Geroski
Dayle H
DH
Aaberg
Thomas M
TM
Edelhauser
Henry F
HF
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003094:Collagen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D012590:Sclera / Q000187:drug effects / Q000378:metabolism*
D004337:Drug Carriers; D003094:Collagen; D002945:Cisplatin