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.
Emory Eye Center, Suite B2600, 1365B Clifton Road NE, Atlanta, GA 30322, USA.
Jake A
JA
Gilbert
Amanda E
AE
Simpson
David E
DE
Rudnick
Dayle H
DH
Geroski
Thomas M
TM
Aaberg
Henry F
HF
Edelhauser
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