title: Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.
abstract: The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.
authors.affiliation: Faculty of Pharmacy, Kindai University.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001682:Biological Availability; D003315:Cornea / Q000378:metabolism; D004221:Disulfiram / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D015195:Drug Design; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D053758:Nanoparticles; D009883:Ophthalmic Solutions; D010316:Particle Size; D011817:Rabbits
chemical_list: D009883:Ophthalmic Solutions; D004221:Disulfiram