Targeted Drug Delivery for Lung Diseases

NHLBI DLD Workshop on Precision Therapeutics Delivery for Lung Diseases: State of the Art Technologies and Lung Biology

The goals of the workshop:

• To bridge the numerous barriers engendered by the multidisciplinary expertise of the biomedical and material sciences researchers working in precision pulmonary drug delivery;
• To improve our understanding of how to best deliver therapeutics to the targeted lung tissues or cells in patients with lung diseases;
• To identify key challenges including identification of cellular and molecular targets, design, and translational development of safe and clinically useful targeted therapeutics;
• To identify the gaps in research and barriers to development that need to be addressed before the promise of precision treatment for lung diseases can be realized;
• To generate recommendations to NHLBI for future research priorities in this area in line with NHLBI Strategic Vision.

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.

Recommendations:

The following high priority research areas were recommended:

• Identify lung diseases and disease processes in adult and pediatric patients that stand to benefit the most from advances in precision drug delivery.
• Identify key cellular and molecular targets for pulmonary drug delivery and relevant biological barriers to drug safe permeation.
• Identify, validate and optimize carriers, routes and regimens in terms of efficacy and safety for specific lung diseases.
• Rapidly identify potentially adverse intracellular and/or systemic off-target effects.
• Balance pros and contras of experimental models and employ their continuum from in vitro and cell culture via animal to studies in isolated human lungs for deciphering biological and design factors that control delivery, cellular addressing, and the fate of drugs and their carriers.
• Realistically gauge the potential and problematic aspects for scalability; targeting preparations amenable to sufficient expansion into large animals and clinical trials.

Opportunities:

• Leverage existing NHLBI-supported resources and programs to address many of the questions above.
• Stimulate new requests for translational applications in this research domain using the programmatic mechanisms that foster multidisciplinary collaboration and advance product development.
• Encourage leveraging organ procurement organizations (OPOs) in the US, which discard ~70-80% of lungs that are deemed not viable for transplant. This resource of human lungs could be ideal for the targeted therapy research community to use in pre-clinical studies.
• Utilize resources from clinical and translational science institutes to understand the regulatory requirements involved for developing targeted therapies and nanomedicine.
• Encourage Food and Drug Administration (FDA) Pre-Investigational New Drug (IND) discussions early in the translational process; take advantage of FDA orphan market opportunities.

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.

Workshop Co-Chairs:

Robert J. Gropler, M.D.

Washington University School of Medicine

Vladimir Muzykantov, M.D., Ph.D.

University of Pennsylvania

Workshop Participants:

Delphine L. Chen, M.D.,

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   

NHLBI Staff:

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