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Lung diseases are leading causes of morbidity, mortality, and health care expenditures. Most of these conditions including pulmonary hypertension (PH), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI)/adult respiratory distress syndrome (ARDS), ischemia-reperfusion (I/R) lung diseases, and chronic obstructive pulmonary disease (COPD) still lack effective, disease modifying pharmacotherapy. Therapeutic utility of many potentially potent drugs, including biotherapeutics, is hampered by inaccessibility of intended targets and off-site adverse effects. In many instances, selective delivery to given cell types, phenotypes, and sub-cellular compartments requires that an agent safely permeates multiple biological barriers in order to achieve the desirable effects. Innovative approaches are urgently needed for mechanistically and spatiotemporally precise pharmacological interventions in these conditions.
In the last two decades, enormous resources have been invested and encouraging progress achieved through the amalgamation of drug delivery research with nanomedicine technologies development. Examples include the design of targeted delivery of drugs and probes employing a variety of nanocarriers, fusion proteins, and other means that combine affinity, masking, sensory, barrier-permeation, and other functionalities. Drug delivery using nanomedicine is an extraordinarily diverse multidisciplinary field that requires bioengineering, pharmaceutical and material sciences, imaging, basic biomedicine, and relevant clinical expertise. To date, precision therapeutics has primarily focused on oncologic applications. However, precision drug delivery for lung diseases is well-positioned to advance, given the emergence of novel drug delivery paradigms and the unique accessibility of pulmonary tissues via airway and vascular routes.
The Division of Lung Diseases (DLD) of the National Heart, Lung and Blood Institute (NHLBI) convened a workshop on September 25-26, 2014 to identify important knowledge gaps and key areas for further development to advance targeted delivery and the effects of drugs and imaging probes in managing and treating lung disease. The workshop facilitated discussions among investigators in the fields of cardiopulmonary diseases, nanotechnologies, and therapeutics design and delivery.
The Workshop specifically addressed the following key areas:
-Lung diseases and disease processes where clinical management may significantly benefit from better targeted therapies including PH, ALI/ARDS, IPF, lung oxidative stress and I/R, and the multiple pathological pathways, cellular, and molecular targets to exploit for precision therapies.
-Approaches for pulmonary drug delivery via the airways including such aspects as design of drug carriers, their tissue distribution, and potential adverse effects, biological barriers, and means for their permeation.
-Drug targeting to the pulmonary vasculature using affinity carriers to endothelial targets, including caveolar and adhesion molecules, to enable interventions in the blood/endothelial interface, specific cellular compartments in the pulmonary endothelium, and across the endothelium.
-Approaches and agents for imaging lung structures, functions, and pathologies, as well as imaging of drug delivery and effects, including imaging of the airways using MRI, imaging molecular signatures of inflammation, and high-resolution CT, PET, and other modalities.
-Principles of design of drug carriers and targeting modalities including polymeric and non-polymeric nanocarriers for diverse routes of administration, priorities of their pre-clinical translation and prospective industrial and clinical development and associated technical, regulatory and socioeconomic challenges and potential avenues for their resolution.
The following high priority research areas were recommended:
The Workshop recommended that parallel paths of basic and clinical research should be taken to advance drug targeting and precision therapy of lung diseases in pediatric and adult diseases, so that bench-to-bedside and bedside-to-bench discoveries can be accomplished.
Robert J. Gropler, M.D.
Washington University School of Medicine
Vladimir Muzykantov, M.D., Ph.D.
University of Pennsylvania
Washington University School of Medicine
Richard Corley, Ph.D.
Pacific Northwest National Laboratory
Bastiaan Driehuys, Ph.D.
Duke University
Robert C. Getts, Ph.D.
Genisphere
Mark T. Gladwin, M.D.
University of Pittsburgh School of Medicine
Justin Hanes, Ph.D.
Johns Hopkins Whiting School of Engineering
Eric A. Hoffman, Ph.D.
University of Iowa
Valerian E. Kagan, Ph.D.
University of Pittsburgh
Gregory Lanza, M.D., Ph.D., FACC
Washington University School of Medicine
Patty J. Lee, M.D.
Yale University
Asrar B. Malik, Ph.D.
University of Illinois at Chicago
Tamara Minko, Ph.D.
Rutgers, The State University of New Jersey
Dana T. Minnick, Ph.D., D.A.B.T., R.A.C.
RTI International
Samir Mitragotri, Ph.D.
University of California, Santa Barbara
Silvia Muro, Ph.D.
University of Maryland
Rahim R. Rizi, Ph.D.
University of Pennsylvania
Jan Schnitzer, M.D.
Proteogenomics Research Institute for Systems Medicine (PRISM)
Rubin Tuder, M.D.
University of Colorado Denver
Neeraj Vij, M.S., Ph.D.
Central Michigan University
Karen L. Wooley, Ph.D.
Texas A&M University
Hing C. Wong, Ph.D.
Altor BioScience Corporation
G. Scott Worthen, M.D.
University of Pennsylvania
James Kiley, Ph.D.
Division of Lung Diseases
Timothy Moore, M.D., Ph.D.
Division of Lung Diseases
Lei Xiao, M.D., Ph.D.
Division of Lung Diseases
Weiniu Gan, Ph.D.
Division of Lung Diseases
Kurt W. Marek, Ph.D.
Office Of Translational Alliances & Coordination