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.

中文翻译：

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金属有机框架NH ₂ -MIL-88（Fe），作为眼用溴莫尼定的载体

我们已经提出了一种金属有机框架（MOF）NH ₂ -MIL-88（Fe），作为一种将药物局部输送到眼睛的新型载体。通过溶剂热合成法制备NH ₂ -MIL-88（Fe）颗粒，并通过粉末X射线衍射，傅立叶变换红外分析，热重分析，电子显微镜和N ₂吸附-脱附测量确定其结构。当溴莫尼定（一种抗青光眼药物）封装到NH ₂ -MIL（Fe）-88（即NH ₂ -MIL-88（Fe）/ Br）中时，该药物的加载量为121.3 µg / mg，并在持续长达12小时。NH ₂-MIL-88（Fe）/ Br表现出粘膜粘附特性​​，并在兔眼上保留长达4小时的时间。因此，在施用NH ₂ -MIL-88（Fe）/ Br后，在长时间的泪液中发现了高浓度的溴莫尼定，与之相比，其生物利​​用度和活性期增加了两倍以上。 Alphagan P是溴莫尼定滴眼剂，已获准用于临床。因此，NH ₂ -MIL-88（Fe）被认为是用于局部递送至眼睛的有前途的载体，其提供了眼用药物的提高的生物利用度。

重要声明

我们建议NH ₂ -MIL（Fe）-88，一种金属有机骨架（MOF），作为眼科药物溴莫尼定的递送载体。NH ₂ -MIL（Fe）-88颗粒具有粘膜粘着性，因此当局部施用于眼睛时，其在眼前间隙中的保留时间延长。颗粒还可以将药物封装在它们的微孔中，通过该微孔可以持续释放药物。因此，当在体内对兔眼进行测试时，与市售的溴莫尼定滴眼剂Alphagan P相比，载有药物的NH ₂ -MIL（Fe）-88颗粒具有增强的眼药生物利用度。