Pulmonary Delivery of Butyrylcholinesterase as a Model Protein to the Lung.

Pulmonary delivery has great potential for delivering biologics to the lung if the challenges of maintaining activity, stability, and ideal aerosol characteristics can be overcome. To study the interactions of a biologic in the lung, we chose butyrylcholinesterase (BuChE) as our model enzyme, which has application for use as a bioscavenger protecting against organophosphate exposure or for use with pseudocholinesterase deficient patients. In mice, orotracheal administration of free BuChE resulted in 72 h detection in the lungs and 48 h in the broncheoalveolar lavage fluid (BALF).

Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells.

Unlabelled: Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles.

Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance.

Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance.

Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery.

Purpose: We evaluated the role of a poly(ethylene glycol) (PEG) surface coating to increase residence times and alter the cellular fate of nano- and microparticles delivered to the lung.

Methods: Three sizes of PRINT hydrogel particles (80 × 320 nm, 1.5 and 6 μm donuts) with and without a surface PEG coating were instilled in the airways of C57/b6 mice.

Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization.

Pulmonary immunization enhances local humoral and cell-mediated mucosal protection, which are critical for vaccination against lung-specific pathogens such as influenza or tuberculosis. A variety of nanoparticle (NP) formulations have been tested preclinically for pulmonary vaccine development, yet the role of NP surface charge on downstream immune responses remains poorly understood. We used the Particle Replication in Non-Wetting Templates (PRINT) process to synthesize hydrogel NPs that varied only in surface charge and otherwise maintained constant size, shape, and antigen loading.

Application of an environmentally sensitive fluorophore for rapid analysis of the binding and internalization efficiency of gene carriers.

Nonviral gene carriers must associate with and become internalized by cells in order to mediate efficient transfection. Methods to quantitatively measure and distinguish between cell association and internalization of delivery vectors are necessary to characterize the trafficking of vector formulations. Here, we demonstrate the utility of nitro-2,1,3-benzoxadiazol-4-yl (NBD)-labeled oligonucleotides for discrimination between bound and internalized gene carriers associated with cells.