In order to understand the effect of charge type on corneal transport of peptides, it is useful to first investigate the mechanism of transport of amino acids across corneal tissue. The transport characteristics of l-[14C]lysine and l-[14C]glutamic acid were based on in vitro flux measurements. Net flux of l-lysine occurs via a sodium-dependent cotransport mechanism (with a coupling ratio of 1:1). The transport of l-lysine involves the Na+-K+-ATPase pump and requires a stereospecific carrier-mediated transport system. The permeability coefficient (P) of l-lysine was decreased from 10.1 ± 0.80 to 2.34 ± 0.75 × 10-6 (cm/s by blocking the active pump and carrier-mediated system. However, l-glutamic acid was apparently absorbed by a passive aqueous transport mechanism which was oubain-insensitive, [Na+]-independent, temperature-insensitive and non-stereospecific. Overall, the cornea was 2-3-fold more permeable to a cation (l-lysine) than an anion (l-glutamic acid). In addition, the negatively charged drug, salicylic acid, was 2.3 times less permeable than the cationic drug, benzylamine.
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