# Inhaled Fasudil and DETA NONOate CAR-Targeted Liposomes for PAH

> **NIH NIH R42** · VASCULAR BIOSCIENCES · 2021 · $1,291,298

## Abstract

Pulmonary arterial hypertension (PAH) affects ~15-50 individuals per million and claims ≥20,000 lives annually
in the United States. It affects every ethnic group, race, age and gender, and devastates high-risk patients
afflicted with HIV, systemic sclerosis, and sickle cell disease. The disease affects more women than men; adult
PAH patients do not live more than five years after the diagnosis. PAH even affects newborn infants and
toddlers: PAH-afflicted children do not survive past their second birthday, if left untreated. Current medications
fail to reduce mortality, extend survival time, or enhance patient quality of life. Many patients do not respond to
existing oral and inhaled anti-PAH drugs; thus, they must receive a continuous intravenous infusion of
prostacyclin analogs, or undergo lung transplantation. Unlike the “emperors of maladies” (cancer and stroke),
PAH has not received much attention from the drug-discovery establishment, so the progress toward
medication development and long-term management of this “orphan” disease has been minimal. Since PAH
affects only a relatively small number of patients, pharmaceutical manufacturers have not made it a priority to
find a cure for PAH, a disease that was first described in the 1950s. In this project, we propose to develop a
targetable and inhalable formulation of fasudil, a rho-kinase inhibitor, and DETA NONOate (DN), a nitric oxide
(NO) donor. We will develop this combination therapy by encapsulating both drugs, fasudil and DN, in
liposomes modified with a cyclic peptide, CAR (CARSKNKDC), which accumulates preferentially in
hypertensive pulmonary arteries. In a series of studies, we have demonstrated that CAR-modified liposomes
containing fasudil and DN reduce the mean pulmonary arterial pressure (mPAP), and this ameliorates various
features of pulmonary arterial remodeling. In this Fast-Track application, we will evaluate the potential for the
clinical translation and commercial development of our targeted liposomal formulation-based combination
therapy for PAH. In Phase I, we will study the effect of the long-term administration of the inhaled CAR-
liposomal formulation of fasudil-plus-DN on pulmonary hemodynamics, lung remodeling, and right ventricle
(RV) hypertrophy, and determine the sensitivity and specificity of assays for detecting nanogram levels of
fasudil and NO in plasma. In Phase II, we will conduct studies to determine the dose-response,
pharmacokinetics and safety of the formulations. The proposed studies will lay the foundation for an FDA IND
application and clinical translation, and will establish the CAR-liposomes of fasudil-plus-DN as a novel and
inhalable therapeutic option for PAH patients that will: a) specifically target the hypertensive pulmonary
vasculature, and b) provide synergistic therapeutic benefits through both the Rho A/Rho kinase and NO donor
pathways, without the additive adverse side effect of systemic vasodilation. Our approach is innovative,
because w...

## Key facts

- **NIH application ID:** 10274778
- **Project number:** 4R42HL151045-02
- **Recipient organization:** VASCULAR BIOSCIENCES
- **Principal Investigator:** Fakhrul Ahsan
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,291,298
- **Award type:** 4N
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274778

## Citation

> US National Institutes of Health, RePORTER application 10274778, Inhaled Fasudil and DETA NONOate CAR-Targeted Liposomes for PAH (4R42HL151045-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274778. Licensed CC0.

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