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Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections

Award Number: R01AI134770
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/24/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections - Project Summary Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections The goal of the proposed research to create new therapeutics targeting multidrug-resistant biofilm infections. These infections are difficult to treat. The refractory nature of biofilm infections make them non-responsive to standard antibiotics, a situation exacerbated by acquired antibacterial resistance. In our research, we have integrated the nanomedicine capabilities of Rotello with wound biofilm expertise of Patel to develop crosslinked nanoemulsions (XNEs) that use a crosslinked polymer network to stabilize nanodroplets of essential oils. These XNEs kill biofilm-based bacteria with minimal effects on host cells and can eradicate biofilms through incorporation of antimicrobials into the oil component of the XNE. XNEs have good efficacy (killing ≥99% of bacteria in biofilms) using the in vivo wound biofilm model developed by Patel. Consistent with other antimicrobial nanomaterials, however, killing is less effective in vivo than in vitro. In our proposed research, Rotello will develop new block copolymers to generate block copolymer XNE (B-XNE) therapeutics. The B-XNEs will then be incorporated into hydrogel wound dressings to provide controlled release of B-XNEs to treat wound infections. B-XNEs and B-XNEs in wound dressings will be tested in vitro and in vivo using realistic and challenging wound biofilm models. Aim 1: Rotello will synthesize block copolymers and use these to parametrically vary size and charge of B-XNEs. These B-XNEs will then be used to carry antibiotics, providing synergistic activity with essential oils. B-XNEs will be screened for activity using luminescent methicillin-resistant Staphylococcus aureus (MRSA) biofilms, and then tested against other bacterial species by Rotello and Patel. Co-culture models employing mammalian cells will be used to downselect agents that maximize antibacterial activity and minimize mammalian cell toxicity. Aim 2: Rotello will incorporate B-XNEs into hydrogels to provide antimicrobial wound dressings. B-XNEs and hydrogels will be co-engineered to provide controlled release of B-XNEs. These B-XNE will be screened using luminescent MRSA to identify promising B-XNE-hydrogel combinations, and further tested as in Aim 1 by Rotello and Patel. Aim 3: Rotello and Patel will use murine wound biofilm models to test B-XNEs and B-XNE wound dressings. These studies will combine parametric pilot experiments using luminescent MRSA by Rotello with full pre-clinical evaluation by Patel with MRSA and Acinetobacter baumannii wound biofilms. Efficacy in these models will be quantified by decreased bacterial counts, enhanced wound healing, and diminished purulence as outcomes.


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 = $377,135 )
2025	2025	UNIVERSITY OF MASSACHUSETTS	101 COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	8	6/23/2025	NON-COMPETING CONTINUATION	$377,135
														Subtotal = $377,135

Issue Date FY: 2024 ( Subtotal = $377,555 )
2024	2024	UNIVERSITY OF MASSACHUSETTS	101 COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	7	6/12/2024	NON-COMPETING CONTINUATION	$377,555
														Subtotal = $377,555

Issue Date FY: 2023 ( Subtotal = $377,967 )
2023	2023	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	6	6/20/2023	NON-COMPETING CONTINUATION	$377,967
2023	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	002	5	9/11/2023	COMPETING CONTINUATION	$105,679
2023	2021	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	001	4	9/11/2023	NON-COMPETING CONTINUATION	-$105,679
														Subtotal = $377,967

Issue Date FY: 2022 ( Subtotal = $393,246 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	001	5	6/29/2022	COMPETING CONTINUATION	$393,246
2022	2021	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	4	6/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $393,246

Issue Date FY: 2021 ( Subtotal = $387,690 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	4	6/11/2021	NON-COMPETING CONTINUATION	$387,690
														Subtotal = $387,690

Issue Date FY: 2020 ( Subtotal = $395,539 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	3	6/11/2020	NON-COMPETING CONTINUATION	$395,539
														Subtotal = $395,539

Issue Date FY: 2019 ( Subtotal = $397,710 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	2	6/21/2019	NON-COMPETING CONTINUATION	$397,710
														Subtotal = $397,710

Issue Date FY: 2018 ( Subtotal = $390,589 )
2018	2018	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	001	1	8/1/2018	NEW	$1,163
2018	2018	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Allergy and Infectious Diseases Research	000	1	7/24/2018	NEW	$389,426
														Subtotal = $390,589

Grand Total All Awards = $3,097,431

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Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections

Award Number: R01AI134770

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/24/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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