# New Inhalation Therapy for COPD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

PROJECT SUMMARY
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States; there
is no curative treatment. Both genetic and biomarker surveys strongly implicate dysregulated TGF-β signaling
as a contributor to COPD development and progression. Excessive TGF-β signaling results in airway
obstruction caused by epithelial thickening and alveolar epithelial cell apoptosis with airspace simplification,
each of which is observed in mouse models and patients with COPD. We recently showed that TGF-β
antagonism with systemic angiotensin receptor blockers (ARB) protected against pulmonary damage in mice
exposed to chronic cigarette smoke (CS) and reversed airspace enlargement in a transgenic mouse model of
emphysema. ARB administered orally provides very little drug delivery to the lungs and also cause significant
systemic side effects. Thus, we have focused on the development of ARB formulations that could be delivered
directly to the lung via inhalation by nebulization. Our pilot data suggests that local administration of an ARB
compound, formulated in a novel “mucus-penetrating particle nanocrystal” (MPP-NC) for inhalation, provides
significantly enhanced lung drug levels (compared to a conventional oral formulation) and effective TGF-β
antagonism, resulting in protection against TGF-β-mediated lung injury. Of note, the ARB MPP-NC
formulations are composed entirely of materials that are generally regarded as safe, thereby making our
approach potentially highly translational. We also introduce an elegantly simple approach to maximize lung
distribution and retention of inhaled therapeutics, namely hypo-osmolar vehicle solutions. We plan to develop
MPP-NC formulations with eight potent FDA-approved ARB drugs and thoroughly characterize in vitro,
followed by screening of promising formulations for TGF-β antagonism in an acute CS-exposed mouse model
of lung injury. The most promising formulations delivered in an optimized hypo-osmolar vehicle solution will be
tested for pharmacokinetics, safety, and therapeutic efficacy following repeated local administration in a
chronic CS-exposed mouse model of COPD.

## Key facts

- **NIH application ID:** 9948731
- **Project number:** 5R01HL136617-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Enid R Neptune
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2017-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948731

## Citation

> US National Institutes of Health, RePORTER application 9948731, New Inhalation Therapy for COPD (5R01HL136617-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948731. Licensed CC0.

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