Ocular Epithelial Models

Abstract

Next to the brain, the eye is probably the most guarded organ against the entry of all but the essential nutrients. This is credited to the simple yet highly efficient protective machinery comprised of rapid removal of the applied dose through drainage (Chrai et al., 1973, 1974) or tear turnover (Mishima et al., 1966); diversion of drugs into the systemic circulation via blood vessels in the conjunctival and the nasal mucosae (Chang and Lee, 1987); a practically impermeable corneal barrier (Sieg and Robinson, 1976); and, to a lesser extent, metabolism of drugs, notably those containing ester (Lee, 1983; Lee et al., 1983a, b), peptide (Stratford and Lee, 1985), and ketone linkages (Ashton et al., 1991b), during and following transport. The net result is that typically less than 1% of the applied dose reaches the anterior segment of the eye (Lee and Robinson, 1986) and that virtually none is available to act on the posterior segment tissues except when under iontophoresis (Lam et al., 1994). It is therefore not surprising that a major activity in ocular drug development has been focused on identifying means to improve ocular drug bioavailability (Lee et al., 1994; Lehr et al., 1994; Naveh et al., 1994; Pleyer et al., 1993; Zimmer et al., 1994). The realization that topically applied drugs can be absorbed systemically (Lee et al., 1993; Liu and Chiou, 1994; Podder et al., 1992) to elicit serious side effects in some instances has provided yet another compelling incentive toward meeting this goal. Through dose reduction in proportion to the gain in ocular absorption, the systemic drug load can be minimized (Potter et al., 1988).