The physical and biochemical barriers of the eye to topical instillation are tear flow drainage, corneal resistance to diffusion, enzymatic degradation in tears and cornea, and flow of aqueous humor. The ocular bioavailability of instilled drug is therefore extremely low for most ophthalmic solutions, and less than about 5% of the drug may reach the anterior chamber of the eye. 1) Usually, poorly soluble drugs are designed as ophthalmic suspensions. However, ocular bioavailability for ophthalmic suspensions is not good, similar to ophthalmic solutions. An ophthalmic lipid emulsion may improve the ocular bioavailability of poorly soluble or lipophilic drugs by increasing drug solubility in the oil droplet and enhancing drug penetration into intraocular tissues.2-4) Ophthalmic lipid emulsion is also promising with respect to its good tolerance, high stability, and ease of manufacturing.Usually, instilled particulate systems such as liposomes, nanoparticles, and lipid emulsions are rapidly eliminated from tear fluid. [5][6][7][8] Mucoadhesive polymers are therefore used to prolong the residence time of particulate carriers in tear fluid. Carbopol, hyaluronic acid, sodium carboxymethylcellulose, chitosan, and Thiomer are possible mucoadhesive polymers. Many researchers have reported that ocular bioavailability is improved and the residence time of drug in tear fluid prolonged with use of such polymers.9-11) Chitosan, a mucoadhesive polymer, is a cationic biopolymer which is generally obtained by alkaline deacetylation of chitin. It is biodegradable and biocompatible, and features excellent tolerance when administered topically onto the cornea.12) Its mucoadhesive properties are based on hydrogen bonding and electrostatic interaction between positive charges of amino groups in chitosan and the negative charges of sialic acid in mucin. Particulate systems coated with chitosan have been developed to improve the absorption of several drugs administered by one of the present authors. [13][14][15] When mucoadhesive particulate systems were instilled, these systems demonstrated significantly increased ocular bioavailability compared to normal formulations. [16][17][18] However, little is known concerning the pharmacokinetic profiles in tear fluid of instilled chitosan-coated particulate formulations. Additionally, little has been reported on ophthalmic lipid emulsions coated by chitosan to improve ocular bioavailability.In this study, we examined the effects of coating of ophthalmic lipid emulsion with chitosan on ocular bioavailability. Indomethacin was incorporated as a model drug in the oil droplets of the emulsions. It is an anti-inflammatory agent widely used for the treatment of post-operative inflammation after cataract surgery.19) The marketed eye drops containing it unfortunately exhibit poor bioavailability. 20) Thus, the objectives of this study were to evaluate the retention of chitosancoated emulsion in tear fluid, and then to compare the ocular bioavailability of this formulation with non-coated emulsion. We ...