评估UiO-66金属有机框架纳米粒子作为肺药物递送应用中的酸敏感载体。,ACS Applied Materials & Interfaces

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评估UiO-66金属有机框架纳米粒子作为肺药物递送应用中的酸敏感载体。
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-08-06 , DOI: 10.1021/acsami.0c10900
Bader M Jarai ₁ , Zachary Stillman ₁ , Lucas Attia ₁ , Gerald E Decker ₂ , Eric D Bloch ₂ , Catherine A Fromen ₁

Affiliation

开发用于肺部递送的新型药物载体对于实现更高的疗效和治疗肺部疾病的一致性，同时限制由替代给药途径引起的脱靶副作用是必要的。金属有机框架（MOF）最近已出现，是一类材料，具有非常适合肺部药物输送的特性，具有化学可调性，高表面积和孔径，可有效装载治疗性货物和深层肺部穿透。UiO-66是一种基于锆和对苯二甲酸的MOF，具有显着的化学和物理稳定性以及潜在的生物相容性。然而，其用作肺部药物递送载体的可行性尚待研究。这里，我们评估了UiO-66纳米颗粒（NPs）作为新型肺部药物递送载体的使用，并评估了缺少接头缺陷在其对本应用的实用性中的作用。我们确定缺少接头缺陷会导致NP空气动力学差异，但对模型和治疗性货物的装载，货物释放，生物相容性或生物分布的影响最小。这是一个关键的结果，因为它表明了UiO-66的坚固稠度，这是肺部药物输送的关键特征，由于性能可变，剂量不一致会给它带来困扰。不仅如此，UiO-66 NP还表现出pH依赖性的稳定性，在细胞外条件下具有抗降解性，在细胞内环境中具有抗降解性。此外，经口气管NPs的体内小鼠评估。肺部递送后，UiO-66 NP在7天的清除之前仍保留在肺部。我们的结果证明了使用UiO-66 NP作为其通过可调NP特性进行肺部药物输送的新平台的可行性，该平台可实现受控的空气动力学和依赖内在化的货物释放，同时显示出显着的肺部生物相容性。

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Evaluating UiO-66 Metal-Organic Framework Nanoparticles as Acid-Sensitive Carriers for Pulmonary Drug Delivery Applications.

Developing novel drug carriers for pulmonary delivery is necessary to achieve higher efficacy and consistency for treating pulmonary diseases while limiting off-target side effects that occur from alternative routes of administration. Metal–organic frameworks (MOFs) have recently emerged as a class of materials with characteristics well-suited for pulmonary drug delivery, with chemical tunability, high surface area, and pore size, which will allow for efficient loading of therapeutic cargo and deep lung penetration. UiO-66, a zirconium and terephthalic acid-based MOF, has displayed notable chemical and physical stability and potential biocompatibility; however, its feasibility for use as a pulmonary drug delivery vehicle has yet to be examined. Here, we evaluate the use of UiO-66 nanoparticles (NPs) as novel pulmonary drug delivery vehicles and assess the role of missing linker defects in their utility for this application. We determined that missing linker defects result in differences in NP aerodynamics but have minimal effects on the loading of model and therapeutic cargo, cargo release, biocompatibility, or biodistribution. This is a critical result, as it indicates the robust consistency of UiO-66, a critical feature for pulmonary drug delivery, which is plagued by inconsistent dosage because of variable properties. Not only that, but UiO-66 NPs also demonstrate pH-dependent stability, with resistance to degradation in extracellular conditions and breakdown in intracellular environments. Furthermore, the carriers exhibit high biocompatibility and low cytotoxicity in vitro and are well-tolerated in in vivo murine evaluations of orotracheally administered NPs. Following pulmonary delivery, UiO-66 NPs remain localized to the lungs before clearance over the course of seven days. Our results demonstrate the feasibility of using UiO-66 NPs as a novel platform for pulmonary drug delivery through their tunable NP properties, which allow for controlled aerodynamics and internalization-dependent cargo release while displaying remarkable pulmonary biocompatibility.

更新日期：2020-09-02

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