# Active Drug Loading to Nanovesicles for Targeted Drug Delivery

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $344,250

## Abstract

Abstract:
Inflammation is the immune response to eliminate invading pathogens to prevent tissue injury, but excessive
vascular inflammation is the pathogenesis of most diseases. Targeting inflammation pathways in vasculature
may be an attractive means to manage the host immune responses for prevention of disease developments. In
this proposal, we choose the mouse lung disease as a model to examine our hypothesis. Bacterial infection
causes acute lung inflammation/injury (ALI) that quickly precipitates acute respiratory distress syndrome (ARDS).
Current therapies are lung-protection ventilation and fluid-conservative management. There is no formally
recommended pharmacological therapy for ALI/ARDS. Despite advances in care devices and efforts to develop
new therapeutics, the mortality is still unacceptably high at 40%. In pathogenesis of ALI/ARDS, vascular
inflammation promotes neutrophil adhesion and transmigration into the lungs. Neutrophils, a type of blood
circulating leukocytes, bind and adhere to activated lung endothelium via several binding molecules between a
neutrophil and an endothelium. Inspired by this unique intercellular interaction we have created nanovesicles
made from the neutrophil membrane. We propose that neutrophil nanovesicles are a new drug delivery
platform for delivering drugs to inflamed mouse lungs to control ALI developments. Based on our
preliminary results on neutrophil nanovesicle production, intravital microscopy and LPS- or bacterium-induced
acute lung injury mouse models, we have demonstrated the feasibility of this proposal, novel concepts and a
great impact in nanomedicine. We propose three aims to test our hypothesis:
Aim 1: To determine the properties of human neutrophil membrane formed nanovesicles required for
endothelial targeting.
Aim 2: Active loading of NF-κB inhibitors inside nanovesicles for improved therapies of mouse ALI
induced by LPS.
Aim 3: Co-delivery of an antibiotic and an anti-inflammation drug by nanovesicles enhances bacterial
killing and resolves host inflammation in a bacterium-induced ALI mouse model.
Completion of this proposal may lead to not only the development of a new delivery system but also shift the
current paradigm in nanomedicine to biology-inspired design of nanotherapeutics.

## Key facts

- **NIH application ID:** 9971534
- **Project number:** 5R01EB027078-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Zhenjia Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2019-07-03 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971534

## Citation

> US National Institutes of Health, RePORTER application 9971534, Active Drug Loading to Nanovesicles for Targeted Drug Delivery (5R01EB027078-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971534. Licensed CC0.

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