Disposition of cyclophosphamide in the rabbit and human cornea.
ABSTRACT Rabbit (dark irides and albino) and human corneas were excised and mounted in a Lucite chamber in order to determine the permeability of cyclophosphamide-14C and to identify its metabolites. The chromatographic scans obtained from the developed thin-layer plates showed only one peak for either rabbit or human corneas which corresponded to cyclophosphamide. By measuring the permeability of cyclophosphamide across the intact cornea, stroma alone, epithelium/stroma, and stroma/endothelium, it was possible to determine the resistance to penetration for each layer. The epithelium was the rate determining barrier, whereas both the stroma and endothelium offered little resistance. The stroma behaves as an inert sieve with drug diffusing through an aqueous media of gel-like mucopolysaccharide interspersed by a matrix of collagen fibrils.
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ABSTRACT: During the past decade liposomes have been investigated extensively for their ability to improve drug utilization by the body, first in the area of chemotherapeutics and most recently in the area of ophthalmology. Liposomes are vesicle-like structures with a concentric series of alternating compartments of aqueous spaces and phospholipid bilayers. To date, liposomes have been found to both promote and reduce ocular drug absorption, indicating that a definite need exists for further studies to evaluate the interplay of drug, liposomes, and the corneal surface in determining the effectiveness of liposomes as vehicles for topically applied ophthalmic drugs. The purpose of this review is to place in perspective the role of liposomes in topical ocular drug delivery. As background material, the factors influencing ocular drug bioavailability and the features of liposomes pertinent to their effectiveness as drug carriers are reviewed.Survey of Ophthalmology 03/1985; 29(5):335-48. DOI:10.1016/0039-6257(85)90109-2 · 3.51 Impact Factor
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ABSTRACT: Existing ocular drug delivery systems are fairly primitive and inefficient, but the stage is set for the rational design of newer and significantly improved systems. The focus of this review is on recent developments in topical ocular drug delivery systems relative to their success in overcoming the constraints imposed by the eye and to the improvements that have yet to be made. In addition, this review attempts to place in perspective the importance of pharmacokinetic modeling, ocular drug pharmacokinetic and bioavailability studies, and choice of animal models in the design and evaluation of these delivery systems. Five future challenges are perceived to confront the field. These are: (a) The extent to which the protective mechanisms of the eye can be safely altered to facilitate drug absorption, (b) Delivery of drugs to the posterior portion of the eye from topical dosing, (c) Topical delivery of macromolecular drugs including those derived from biotechnology, (d) Improved technology which will permit non-invasive monitoring of ocular drug movement, and (e) Predictive animal models in all phases of ocular drug evaluation.Journal of ocular pharmacology 02/1986; 2(1):67-108. DOI:10.1089/jop.1986.2.67
- Clinical Pharmacokinetics 05/1990; 18(4):255-69. · 5.49 Impact Factor