# Dual drug delivery to lung/blood interface in respiratory infections.

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $698,173

## Abstract

Two pulmonary interfaces play the key role in respiratory infections, both bacterial and viral (e.g.,
COVID19). The invaders enter via external interface formed by airway and alveolar epithelial cells.
The adjacent internal vascular interface formed by endothelial cells recruits and other host defense
including neutrophils (PMN) to invasion site. Overzealous PMN hurt endothelium. Emerging reports
implicate this collateral damage in COVID19 poor outcomes. Anti-inflammatory drugs could alleviate
this issue, but pose risk of infection spread. To protect lungs from "friendly fire" without inhibiting PMN
fighting infection we target nanocarriers loaded with anti-inflammatory agents using affinity ligands
binding to specific epitopes on the pulmonary endothelium. Fortuitously, pilot screening of ~30
nanoparticles revealed that after IV injection some formulations lacking affinity ligands accumulate in
the PMN in inflamed lungs. We want to use these findings for dual drug delivery to endothelium and
adjacent PMN. In Aim 1, we will interrogate the nano-scale interface between the surface of PMN-
tropic nanocarriers and microenvironment to elucidate the mechanism of PMN uptake. In Aim 2, we
will investigate effect of endothelial- and PMN-tropic nanocarriers on the micro-scale interface of
pulmonary microvasculature. These studies will elucidate the fundamental mechanisms by which
nanocarrier material properties dictate opsonization, and in turn tropism for PMNs, the most important
leukocyte in pneumonia. We will determine how nanocarriers localize to the two key cell types in
defense against pneumonia, thus creating a platform drug delivery system to treat both bacterial and
viral pneumonia.

## Key facts

- **NIH application ID:** 10813768
- **Project number:** 5R01HL157189-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Vladimir R Muzykantov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $698,173
- **Award type:** 5
- **Project period:** 2021-04-20 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813768

## Citation

> US National Institutes of Health, RePORTER application 10813768, Dual drug delivery to lung/blood interface in respiratory infections. (5R01HL157189-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813768. Licensed CC0.

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