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Robust Delivery of Antimicrobial Peptides

Award Number: R03AI154314
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: 06/10/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Robust Delivery of Antimicrobial Peptides - Project Summary This project explores the development of bicontinuous microemulsions (BEs) as topical drug delivery systems for antimicrobial peptides (AMPs), as an alternative therapy to treat wound infections. This study addresses the missions of both the NIH’s NIBIB and NIAID research programs through: 1) the development of a novel drug delivery technology, and 2) a new approach to combat chronic wound infections exacerbated by antibiotic-resistant microorganisms. Wound infections are a major problem due to the increased occurrence of antibiotic-resistant microorganisms, which are attributable to $20 billion annually in excess health care costs, $35 billion in societal costs, and 8 million days of extended hospitalization stays in the US. AMPs can kill microbial pathogens that cause wound infections (e.g., methicillin-resistant Staphylococcus aureus [MRSA]) through disruption of negatively charged biomembranes, producing pores that allow leakage of cytoplasmic fluids; however, AMPs must be delivered in a highly folded form to be effective and previous studies have not addressed this need. Thus, this study proposes to develop BEs as systems for encapsulation of AMPs in their folded state and delivery to wound surfaces. BEs are optically clear, homogeneous, and thermodynamically stable biomembrane mimetic systems. They possess unique drug-delivery properties compared to other membrane-based systems, including large-volume fractions of water and oil (~40%) that allow co-solubilization of other drugs. Preliminary studies demonstrate that the AMP melittin when encapsulated into BEs can reside in a highly folded state (>90% -helix) and high concentrations (1-10 g/L) are achievable. Several important hypotheses will be tested, including that AMP-loaded BE solutions are effective antimicrobial agents with activity strongly controlled by the extent of AMP folding. The Specific Aims are to 1) demonstrate that four diverse AMPs can be incorporated into several different biocompatible BE systems at high (biologically relevant) concentrations and degrees of folding; 2) show that BEs loaded with AMPs and antiseptic agents such as chlorhexidine (derived in Aim 1) can serve as robust topical preparations for treatment of wound infections. For Aim 1, the relationship between AMP folding and BE properties will be determined through novel methods, including circular dichroism and small-angle neutron scattering. Aim 2 will provide measurements of minimum inhibitory and bactericidal concentration against several representative microorganisms encountered in wounds (including MRSA), cell cytotoxicity (hemolysis) activity and protection of BE-encapsulated AMPs from proteolysis. The results will provide a basis for future clinical applications to use BEs as a drug delivery system for improved activity and/or stability of cell-penetrating peptides. Other applications include adsorption to surfaces of medical devices for antimicrobial coatings and delivery of radiolabeled AMPs for bioimaging.


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: 2024 ( Subtotal = -$8,051 )
2024	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Allergy and Infectious Diseases Research	000	2	3/12/2024	NON-COMPETING CONTINUATION	-$8,051
														Subtotal = -$8,051

Issue Date FY: 2021 ( Subtotal = $65,934 )
2021	2021	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	000	2	5/6/2021	NON-COMPETING CONTINUATION	$65,934
														Subtotal = $65,934

Issue Date FY: 2020 ( Subtotal = $66,111 )
2020	2020	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	000	1	6/9/2020	NEW	$66,111
2020	2020	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	001	1	6/22/2020	NEW	$0
														Subtotal = $66,111

Grand Total All Awards = $123,994

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Robust Delivery of Antimicrobial Peptides

Award Number: R03AI154314

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: 06/10/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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