Nebulization of Model Hydrogel Nanoparticles to Macrophages at the Air-Liquid Interface.

Nanoparticle evaluation within the pulmonary airspace has increasingly important implications for human health, with growing interest from drug delivery, environmental, and toxicology fields. While there have been widespread investigations of nanoparticle physiochemical properties following many routes of administration, nanoparticle behavior at the air-liquid interface (ALI) is less well-characterized. In this work, we fabricate two formulations of poly(ethylene)-glycol diacrylate (PEGDA)-based model nanoparticles to establish an workflow allowing evaluation of nanoparticle charge effects at the ALI.

A Pediatric Upper Airway Library to Evaluate Interpatient Variability of In Silico Aerosol Deposition.

The airway of pediatric patients' changes through development, presenting a challenge in developing pediatric-specific aerosol therapeutics. Our work aims to quantify geometric variations and aerosol deposition patterns during upper airway development in subjects between 3.5 months-6.

Prediction of transport, deposition, and resultant immune response of nasal spray vaccine droplets using a CFPD-HCD model in a 6-year-old upper airway geometry to potentially prevent COVID-19.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the angiotensin-converting-enzyme-2-rich region, i.e., the olfactory region (OR), in the nasal cavity of a 6-year-old female to possibly prevent corona virus disease 19 (COVID-19).

Prediction of Transport, Deposition, and Resultant Immune Response of Nasal Spray Vaccine Droplets using a CFPD-HCD Model in a 6-Year-Old Upper Airway Geometry to Potentially Prevent COVID-19.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the Angiotensin-converting enzyme 2-rich region (i.e., the olfactory region (OR)) in the nasal cavity of a 6-year-old female to possibly prevent COVID-19.

Spatial aerosol deposition correlated to anatomic feature development in 6-year-old upper airway computational models.

The upper airways of children undergo developmental changes around age 6, yielding differences between adult and pediatric anatomies. These differences include the cricoid ring area shape, the location of narrowest constriction, and the angle of the epiglottis, all of which are expected to alter local fluid dynamic profiles and subsequent upper airway deposition and downstream aerosol delivery of inhaled therapeutics. In this work, we quantify "pediatric"-like and "adult"-like geometric and fluid dynamic features of two computed tomography (CT)-scan derived models of 6-year-old upper airways in healthy subjects and compare to an idealized model.

Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases.

Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells.

Check the gap: Facemask performance and exhaled aerosol distributions around the wearer.

Current facemask research focuses on material characterization and efficiency; however, facemasks are often not tested such that aerosol distributions are evaluated from the gaps in the sides, bottom, and nose areas. Poor evaluation methods could lead to misinformation on optimal facemasks use; a high-throughput, reproducible method which illuminates the issue of fit influencing aerosol transmission is needed. To this end, we have created an in vitro model to quantify particle transmission by mimicking exhalation aerosols in a 3D printed face-nose-mouth replica via a nebulizer and quantifying particle counts using a hand-held particle counter.

Evaluating Regional Pulmonary Deposition using Patient-Specific 3D Printed Lung Models.

Development of targeted therapies for pulmonary diseases is limited by the availability of preclinical testing methods with the ability to predict regional aerosol delivery. Leveraging 3D printing to generate patient-specific lung models, we outline the design of a high-throughput, in vitro experimental setup for quantifying lobular pulmonary deposition. This system is made with a combination of commercially available and 3D printed components and allows the flow rate through each lobe of the lung to be independently controlled.

Realizing Lobe-Specific Aerosol Targeting in a 3D-Printed Lung Model.

Delivery of aerosols to isolated lobes of the lungs would be beneficial for diseases that have lobe-specific effects, such as cancer, pneumonia, and chronic obstructive pulmonary disorder. Recent computational fluid-particle dynamic (CFPD) modeling has demonstrated that in low flow rates, the inlet location of a particle at the mouth dictates the lobe into which it will deposit. However, realization of this lobe-specific deposition has yet to be attempted experimentally or in the clinic.