The importance of the conjunctival/scleral pathway as a route of entry into the ciliary body, and in particular uptake and deposition by vessels, was investigated. A constant concentration of methazolamide analogs as well as 6-carboxyfluorescein (6-CB) and rhodamine B (RB) was maintained on either the cornea or the conjunctiva/sclera tissue, the latter excluding the cornea. The solutions were applied with the use of a cylindrical well affixed to the cornea of an anesthetized white rabbit. After two hours, concentrations of drug or dye were measured in cornea, aqueous humor or iris/ciliary body for both routes of entry. Confocal microscopy methods were used to determine reflected fluorescence images for 6-CB and RB. Carbonic anhydrase inhibition, partitioning, solubility and intraocular pressure (IOP) measurements were also determined. Permeability calculations were estimated for drug diffusing against aqueous flow within the posterior chamber. The conjunctival/scleral route of entry produced higher iris/ciliary body concentrations for all compounds except for the lipophilic RB. Confocal microscopy results suggested that drug is gaining entry into the ciliary body through vessel uptake in the sclera. Following entry of drug into the conjunctival/scleral tissue, a significant portion enters scleral vessels and deposits within the ciliary body. Calculations are given that indicate that once drug penetrates the cornea it is highly unlikely drug diffuses through the pupil against aqueous flow to enter the posterior chamber and reach the ciliary body.

Immobilization of bovine serum albumin (BSA) on oxidized cellulose (OC) containing carboxylic groups, a biocompatible and bioresorbable polymer, was investigated in water and different buffer solutions (pH 2-7) at 5 degrees C. The maximum amounts of BSA loaded on OC in pH 2, 3, 4, 6, and 7 buffer media were 9.82, 10.52, 8.86, 9.16, 6.05, and 2.69% (w/w), respectively. In water, the corresponding value was 9.82%. The release study was performed on powder, pellet and suspension (in castor and sesame oils) dosage forms of OC-BSA immobilization products prepared in water and pH 2 buffer, in pH 7.4 phosphate buffer at 37 degrees C. The results revealed the release of BSA to be the fastest from oil suspensions, intermediate from powders, and slowest from pellets. In conclusion, the results presented suggest that OC has the potential to be used as an immobilizing matrix for BSA and other proteins in water and pH 2-4 buffer solutions.

No abstract