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Controlled antibiotic delivery vehicle for treatment of aggressiveperiodontitis

Award Number: R21DE032153
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Controlled antibiotic delivery vehicle for treatment of aggressiveperiodontitis - PROJECT SUMMARY/ABSTRACT Aggressive forms of periodontitis associated with Aggregatibacter actinomycetemcomitans (Aa) are often difficult to treat with traditional means (scaling and root planing, in combination with systemic antibiotics). During infection, Aa produces a leukotoxin (LtxA) that kills host immune cells, thus reducing the host’s ability to clear the infection. Although an association between LtxA expression levels and pathogenicity of Aa has been well documented, particularly in adolescent patients, and the mechanisms by which LtxA kills host cells have been well studied, few new treatment options have been developed in recent years. We propose that LtxA represents an ideal therapeutic target that could be exploited to develop next generation therapeutics for Aa infections in juveniles. The long-term goal of the PI is to develop LtxA-focused therapeutics for the treatment of Aa. The overall objective of this project is to construct a liposome-based, LtxA-responsive antibiotic delivery vehicle to treat Aa infections. The general hypothesis is that LtxA will enable antibiotic release only in the presence of pathogenic (LtxA- expressing) strains of Aa. The general hypothesis will be tested via the following specific aims: (1) Optimize liposome composition to promote LtxA adsorption and LtxA-mediated disruption and (2) Determine the therapeutic liposome concentrations necessary to enhance host cell survival. In Aim 1, we will optimize the composition of the liposome to enhance LtxA-mediated antibiotic release and LtxA adsorption. In Aim 2, we will test the effect of the liposomes on host cell survival in a co-culture model of infection. At the successful completion of the proposed research, the expected outcome is a novel therapeutic option to treat Aa infections in adolescents. The innovation of the proposed work lies in its use of LtxA as a therapeutic target, as well as the development of a controlled antibiotic delivery vehicle for the treatment of aggressive periodontitis. These results will provide a strong basis for the future development of LtxA-focused therapeutics, which is expected to have a significant impact on the clinical treatment of Aa-associated infections in juveniles by providing additional, non- surgical options. This research aligns with NIDCR’s mission to improve oral health through its development of a new treatment for periodontal infections.


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	2024	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Oral Diseases and Disorders Research	000	2	12/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $192,046 )
2024	2024	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Oral Diseases and Disorders Research	001	2	6/18/2024	NON-COMPETING CONTINUATION	$19,205
2024	2024	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Oral Diseases and Disorders Research	000	2	2/29/2024	NON-COMPETING CONTINUATION	$172,841
														Subtotal = $192,046

Issue Date FY: 2023 ( Subtotal = $216,447 )
2023	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Oral Diseases and Disorders Research	000	1	2/23/2023	NEW	$216,447
														Subtotal = $216,447

Grand Total All Awards = $408,493

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Controlled antibiotic delivery vehicle for treatment of aggressiveperiodontitis

Award Number: R21DE032153

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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