A Study of Water-Spread Polymer Micelles on Water Surface: Toward Developing a First-in-Kind Polymer Lung Surfactant Therapy

Purdue University, West Lafayette IN

Investigators

Abstract

Every year around 200,000 patients in the US are diagnosed with Acute Respiratory Distress Syndrome (ARDS) as a result of such causes as viral infection (e.g., COVID-19), physical trauma, and inhalation of chemicals. Patients diagnosed with ARDS (critically low blood oxygenation levels) face a staggering >40% mortality rate. The use of animal-derived lung surfactant replacement therapy that has been used to treat certain respiratory conditions has not been successful in treating ARDS. Therefore, there is dire need for an effective therapeutic that goes beyond current treatments (mechanical ventilation). The investigator’s laboratory is pioneering a transformative first-in-kind “Polymer Lung Surfactant (PLS)” therapy that is composed of a block copolymer and can address limitations of conventional animal-derived lung surfactant therapeutics. By studying their fundamental behavior, advances can be made in the development of a PLS with the hope of ultimately translating this research to improvements in human health outcomes. Lung surfactant replacement therapy is one of the greatest achievements in interfacial science research. Each year in the US alone, this lung surfactant technology saves over 30,000 newborns suffering from deficiency of endogenous lung surfactant. Adults can suffer from similar symptoms (ARDS) when the function of their native lung surfactant becomes impaired due to injury to lung parenchyma. Unfortunately, the surfactant replacement therapy which is used to treat neonates with insufficient lung surfactant stores has not been shown to be effective for ARDS. It has been discovered that micelles derived from a synthetic amphiphilic block copolymer, poly(styrene)-poly(ethylene glycol) (PS-PEG), show great promise for the treatment of ARDS. A greater understanding of the fundamental science of the interfacial mechanical and transport behavior of water-spread block copolymers is required for further advancement of this technology. This is the gap that this award aims to fill. Specifically, the experiments provide understanding on the molecular origin of the unique surface mechanical behavior of water-spread PS-PEG micelles on water surface (toward further optimization of PLS formulations). Surface rheological behavior of water-spread PS-PEG micelles (to understand their unique protein resistant behavior) will be studied. Interfacial flow and coating properties of PS-PEG micelle solutions through lung airways (which will help optimize PLS delivery processes) will be investigated. This award provides multidisciplinary training for graduate and undergraduate students involved to learn state-of-the-art concepts and skills in interfacial engineering. Available campus resources are used to enhance recruitment of underrepresented/minority undergraduate students for this project. Local high school students are provided with research experience opportunities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.