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.

PEGDA-based nanogels have been used in numerous applications, but their degradation rates have not been explored. We determine the degradation rates for multiple formulations and demonstrate key differences in degradation rates relative to bulk gels.

The COVID-19 pandemic caused by the global spread of the SARS-CoV-2 virus has led to a staggering number of deaths worldwide and significantly increased burden on healthcare as nations scramble to find mitigation strategies. While significant progress has been made in COVID-19 diagnostics and therapeutics, effective prevention and treatment options remain scarce. Because of the potential for the SARS-CoV-2 infections to cause systemic inflammation and multiple organ failure, it is imperative for the scientific community to evaluate therapeutic options aimed at modulating the causative host immune responses to prevent subsequent systemic complications. Harnessing decades of expertise in the use of natural and synthetic materials for biomedical applications, the biomaterials community has the potential to play an especially instrumental role in developing new strategies or repurposing existing tools to prevent or treat complications resulting from the COVID-19 pathology. Leveraging microparticle- and nanoparticle-based technology, especially in pulmonary delivery, biomaterials have demonstrated the ability to effectively modulate inflammation and may be well-suited for resolving SARS-CoV-2-induced effects. Here, we provide an overview of the SARS-CoV-2 virus infection and highlight current understanding of the host’s pulmonary immune response and its contributions to disease severity and systemic inflammation. Comparing to frontline COVID-19 therapeutic options, we highlight the most significant untapped opportunities in immune engineering of the host response using biomaterials and particle technology, which have the potential to improve outcomes for COVID-19 patients, and identify areas needed for future investigations. We hope that this work will prompt preclinical and clinical investigations of promising biomaterials-based treatments to introduce new options for COVID-19 patients.

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