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 ...
A diffusion model of ocular pharmacokinetics was used to estimate the effects of pathological conditions on ocular pharmacokinetics. In vivo rabbit data after topical instillation of ciprofloxacin and ofloxacin were compared with the simulated concentrations in the aqueous and vitreous humors. The barrier capacity of the surrounding membranes such as the retina/choroid/sclera (RCS) membrane and the cornea was characterized by dimensionless Sherwood number derived by the pseudo-steady state approach (PSSA). We assumed the barrier capacity decreased by inflammation; when the barrier capacity of the RCS membrane and the cornea was assumed to be one-tenth for the RCS membrane and a half for the cornea respectively, the in vivo data agreed with the simulated profile without contradiction. The drug concentration gradient simulated in the vitreous body near the RCS membrane was more significant in the inflamed eyes than in the normal eyes, suggesting that the elimination of the drugs from the RCS membrane was enhanced by inflammation. The present diffusion model can better describe the ocular pharmacokinetics in both normal and diseased conditions.
A novel type of temperature‐responsive hydrogel with sensitive release performance of an encapsulated compound was obtained. The temperature‐responsive hydrogel with a sensitive state change between 32 °C and 29 °C was prepared by physically crosslinking chitosan with a polyanion of tripolyphosphate and linear poly(N‐isopropylacrylamide) (PNIPAAm). Cyanocobalamin was used as a model drug and was encapsulated in the prepared hydrogel. The swelling ratio and release behavior of cyanocobalamin were evaluated. Hydrogels containing 3.0% chitosan and 3.0% PNIPAAm had the best swelling ratio and the maximum amount of released encapsulated cyanocobalamin. The amount of released cyanocobalamin was quantified at 25 °C and 40 °C to evaluate the release behavior. The encapsulated cyanocobalamin remained within the hydrogels at 25 °C and was rapidly released at 40 °C. After 1 min at 40 °C, the released amount was approximately 50% of the encapsulated cyanocobalamin. The temperature‐responsive hydrogels obtained have good performance for use in drug delivery systems. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46732.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.