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Spreading of Aqueous Surfactant Solutions on Entangled Aqueous Polymer Solutions: Development of Self-Dispersing Aerosolized Drug Carriers for Delivery in Obstructed Lungs
In collaboration with the groups of Stephen Garoff (Carnegie Mellon Physics), Todd Przybycien (Carnegie Mellon Chemical Engineering and Biomedical Engineering) and Timothy Corcoran (University of Pittsburgh School of Medicine), we are developing surfactant formulations to enhance drug delivery to diseased lungs. Inhaled aerosol medications offer an opportunity to directly treat sites of disease within the lung. Current delivery techniques rely mostly on aerodynamic mechanisms to disperse and distribute these medications inside the lung after inhalation. The elements of obstruction common to lung diseases such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease (COPD) can decrease ventilation in portions of the lung, preventing aerosol drugs from reaching these zones. The unusual aerodynamics associated with obstructive disease can also cause very non-uniform deposition patterns, further limiting penetration of active drug. Poor drug distribution ultimately limits their efficacy. For example, the inhaled antibiotics used to treat bacterial infections associated with cystic fibrosis lung disease often provide successful suppression of infection but rarely provide eradication. Drug resistance has also been associated with these therapies likely due to the consistent delivery of sub-therapeutic doses at sites of infection. Pulmonary bacterial infections are a major source of morbidity and mortality in cystic fibrosis. Reaching more sites of infection with therapeutic doses of drug would improve the efficacy of inhaled antibiotic therapies, providing immediate benefit to the 30,000 Americans afflicted with cystic fibrosis lung disease. Our goal here is to develop novel self-dispersing platforms for inhaled antibiotics that will provide improved drug distribution and improved performance in the treatment of bacterial infections associated with cystic fibrosis (CF) lung disease. We propose that adding certain surfactants or low surface tension fluids to inhaled medications will promote the formation of self-dispersing medicated films in the lung. These films will spread medications throughout the airways improving dose uniformity and increasing the dose of medication delivered to regions of reduced ventilation.
Our work on airway mucus obstruction models based on entangled aqueous mucin or synthetic polymer solutions has shown that surface tension gradients established by surfactant adsorbing from deposited droplets drive significant spreading of the aqueous drops over the aqueous subphase. A rapid convective spreading process produces a quasi-static aqueous lens or duplex film on the aqueous subphase, similar to the spreading of a drop on an immiscible subphase. Such observations are leading to detailed investigations of the transport of surfactants across moving contact lines and along the subphase surface.
A.L. Marcinkowski, S. Garoff, R.D. Tilton, J.M. Pilewski, T.E. Corcoran, “Post-deposition dispersion of aerosol medications using surfactant carriers,” Journal of Aerosol Medicine and Pulmonary Drug Delivery 21, 361-370 (2008). DOI: 10.1089/jamp.2008.0699
K. Koch, B. Dew, T.E. Corcoran, T. M. Przybycien, R.D. Tilton, S. Garoff, “Surface tension gradient driven spreading on aqueous mucin solutions: a possible route to enhanced pulmonary drug delivery,” Molecular Pharmaceutics 8, 387-394 (2011). dx.doi.org/10.1021/mp1002448
R. Sharma, R. Kalita, E. Swanson, T. Corcoran, S. Garoff, T.M. Przybycien, R.D. Tilton “Autophobing on liquid subphases driven by interfacial transport of amphiphilic molecules,” Langmuir 28, 15212−15221 (2012). DOI 10.1021/la303639w
R. Sharma, T. Corcoran, S. Garoff, T.M. Przybycien, E. Swanson, R.D. Tilton, “Quasi-immiscible spreading of aqueous surfactant solutions on entangled aqueous polymer solution subphases,” ACS Applied Materials and Interfaces. DOI: 10.1021/am400762q