Enhanced ocular efficacy of topically-delivered dorzolamide with nanostructured mucoadhesive microparticles

• Published in: International journal of pharmaceutics Vol. 522; no. 1-2; pp. 66 - 73
• Main Authors: Park, Chun Gwon, Kim, Young Kook, Kim, Se-Na, Lee, Seung Ho, Huh, Beom Kang, Park, Min-A, Won, Hyein, Park, Ki Ho, Choy, Young Bin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.04.2017
• Subjects: Adhesives; Administration, Ophthalmic; Administration, Topical; Animals; Carbonic Anhydrase Inhibitors - administration & dosage; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Dorzolamide; Drug Compounding; Glaucoma; Intraocular pressure; Intraocular Pressure - drug effects; Lactic Acid; Male; Microparticles; Mucoadhesion; Mucous Membrane; Nanofibers; Nanostructures; Ophthalmic Solutions; Particle Size; Polyglycolic Acid; Propylene Glycol; Rabbits; Solubility; Sulfonamides - administration & dosage; Sulfonamides - chemistry; Sulfonamides - pharmacology; Thiophenes - administration & dosage; Thiophenes - chemistry; Thiophenes - pharmacology; Glaucoma; Nanostructures; Mucoadhesion; Microparticles; Dorzolamide; Intraocular pressure
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.02.035

[Display omitted] Dorzolamide eye drops are widely prescribed to reduce intraocular pressure (IOP) in the treatment of ocular hypertension and glaucoma. However, in an eye drop formulation, dorzolamide is rapidly cleared from the preocular space, hence requiring multiple daily administrations. Here, we sought to increase the preocular retention of dorzolamide using nanostructured, mucoadhesive microparticles (MUCO_NM) as carriers for topical delivery to the eye. MUCO_NM were prepared by freeze-milling dorzolamide-loaded, electrospun nanofibers composed of poly(lactic-co-glycolic acid) and polyethylene glycol. The microparticles were embedded in a rapidly-dissolving tablet of polyvinyl alcohol. To assess in vivo efficacy, the MUCO_NM were administered topically to the eyes of rabbits, and IOP was measured and compared to that in eyes treated with Trusopt®, a marketed eye drop of dorzolamide. The MUCO_NM showed a 35% greater maximum IOP decrease and a>2-fold increase in the duration of the IOP decrease, compared to Trusopt®. This enhanced efficacy was comparable to that obtained with a single administration of 4 drops of Trusopt® or 2 administrations of Trusopt® at a 4-h interval. Our findings suggest that this MUCO_NM preparation is a promising carrier for topical delivery of dorzolamide to the eye, with enhanced drug efficacy and the potential to reduce administration frequency.