Development and Characterization of Quercetin-Loaded Microparticles Via Spray Drying for Pulmonary Drug Delivery Applications

Pulmonary inflammation is associated with respiratory disorders such as pulmonary arterial hypertension and chronic obstructive pulmonary disease. A hallmark of these diseases is an increase in reactive oxygen species in the body, leading to further inflammation and acerbation of these diseases. Fortunately, a class of natural products termed plant-derived flavonoids have been found to alleviate inflammation and oxidative stress in lung tissue, making them promising therapeutic agents for the treatment of pulmonary diseases. Flavonoids are accessible and cost-effective, with quercetin being one of the most commonly consumed flavonoids in the human diet. Despite its therapeutic potential, the efficacy of quercetin is limited due to its poor water solubility, thereby limiting its oral bioavailability. This can be overcome through the encapsulation of quercetin in polymeric-based nanoparticles (NP) and microparticles (MP) for localized delivery to the lungs. Both NP and MP can increase the bioavailability of querc­etin while lowering its dosage amount and frequency. Quercetin-loaded nanoparticles (Q-NP) were formulated via nanoprecipitation and tested for their size, homogeneity, and drug loading. The particles were <200 nm in diameter, with a low polydispersity index, and high drug loading. An antioxidant assay was used to confirm that Q-NP retained high antioxidant properties of quercetin. Quercetin-loaded nanocomposite microparticles (Q-nCmP) were successfully prepared by spray-drying Q-NP to formulate a dry powder aerosol. The Q-nCmP demonstrated desirable morphology and aerosol dispersion properties, high drug loading, and were successfully redispersed­ back into parent Q-NP formulation. Our ongoing research aims to further the development of effective and safe therapies for lung inflammation and chronic respiratory disorders.