Biophysical Characterization of Nanoparticle Interactions with Lung Surfactant Models for Enhanced Pulmonary Drug Delivery
Abstract
Inhalable nanoparticles for drug delivery has shown promising results in the treatment of lung disease. The impact of these small sized drug carriers on the lungs is remains unclear. One of the first barriers that nanoparticles will encounter upon inhalation is the lung surfactant that lines each alveolus. This is a single molecule layer of lipids and proteins that forms at the air-water interface on top of the alveolar lining fluid. Its main role is to lower surface tension preventing the collapse of the alveoli during the breathing cycle. Impairing surfactant function results in collapse of the alveolar sacs leading to respiratory distress. The aim of the thesis was to use in vitro studies to identify which components of lung surfactant that are potentially impacted or influenced by the presence of nanoparticles. This was conducted using a model system for lung surfactant made up for phosphatidylcholine, phosphatidylglycerol and the neutral lipid cholesterol. This was compared to a clinical surfactant BLES that is used in surfactant replacement therapy. Surface activity was measured using a Langmuir trough with two Teflon barriers to mimic the air-water interface and compress the surfactant monolayer. Imaging of the monolayer was conducted with Brewster angle microscopy to visualize changes in the organization of the surfactant models. Gelatin and polyisobutylcyanoacrylate nanoparticles are both biocompatible materials that have been tested for inhalable drug delivery and are used in these experiments. In vitro testing was done to evaluate three different methods of adding nanoparticles to the surfactant monolayer to develop a better in vitro model to study nanoparticle surfactant interactions. These nanoparticles were either mixed with surfactant before application on the trough, added to the subphase or sprayed from the air as dry powder. Cholesterol was found to play a major role in nanoparticle-surfactant interactions by enhancing the formation of spike-like structures from the surfactant monolayer. The Langmuir trough was shown to be a useful tool for studying in vitro interactions. Further optimization of the spraying dry powder nanoparticles onto the Langmuir trough can potentially be a useful tool in vitro tool to predict potentially harmful in vivo effects
Description
Keywords
Biophysics
Citation
Lai, P. (2017). Biophysical Characterization of Nanoparticle Interactions with Lung Surfactant Models for Enhanced Pulmonary Drug Delivery (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25135