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Active Drug Loading to Nanovesicles for Targeted Drug Delivery

Award Number: R01EB027078
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Active Drug Loading to Nanovesicles for Targeted Drug Delivery - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	3/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	1/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $344,250 )
2023	2023	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	3/8/2023	NON-COMPETING CONTINUATION	$344,250
														Subtotal = $344,250

Issue Date FY: 2022 ( Subtotal = $344,250 )
2022	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	5/31/2022	NON-COMPETING CONTINUATION	$34,425
2022	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	2/25/2022	NON-COMPETING CONTINUATION	$309,825
														Subtotal = $344,250

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	1/26/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $344,250 )
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	3/5/2020	NON-COMPETING CONTINUATION	$344,250
														Subtotal = $344,250

Issue Date FY: 2019 ( Subtotal = $327,555 )
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	7/3/2019	NEW	$327,555
														Subtotal = $327,555

Grand Total All Awards = $1,360,305

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Active Drug Loading to Nanovesicles for Targeted Drug Delivery

Award Number: R01EB027078

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/03/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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