Metal-organic frameworks, NH₂-MIL-88(Fe), as carriers for ophthalmic delivery of brimonidine

We have proposed a metal-organic framework (MOF), NH₂-MIL-88(Fe), as a novel carrier for topical drug delivery to the eye. The NH₂-MIL-88(Fe) particles were prepared via a solvothermal synthesis method and their structure was confirmed by powder X-ray diffraction, Fourier transform infrared analysis, thermogravimetric analysis, electron microscopy, and N₂ adsorption-desorption measurements. When brimonidine, an anti-glaucoma medicine, was encapsulated into NH₂-MIL(Fe)-88 (i.e., NH₂-MIL-88(Fe)/Br), the drug was loaded at 121.3 µg/mg and released in a sustained manner for up to 12 h. The NH₂-MIL-88(Fe)/Br exhibited mucoadhesive properties and remained on rabbit eyes for a period of up to 4 h. Consequently, a high concentration of brimonidine was found in tears for a prolonged period after the administration of NH₂-MIL-88(Fe)/Br, which resulted in a greater than two-fold increase in drug bioavailability and activity period compared with those of Alphagan P, which are brimonidine eye drops already approved for clinical use. Hence, NH₂-MIL-88(Fe) is suggested to be a promising carrier for topical delivery to the eye that provides enhanced bioavailability of ocular drugs.

Statement of significance: We suggest NH₂-MIL(Fe)-88, a type of metal-organic frameworks (MOFs), as delivery carriers of an ophthalmic drug, brimonidine. The NH₂-MIL(Fe)-88 particles possess a mucoadhesive property, hence prolonged retention in the preocular space when topically administered to the eye. The particles can also encapsulate the drug in their micro-pores, through which the drug can be released in a sustained manner. Therefore, when tested to rabbit eyes in vivo, the drug-loaded NH₂-MIL(Fe)-88 particles were shown to enhance the ocular drug bioavailability, as compared with Alphagan P, the marketed eye drops of brimonidine.