Controlled antibiotic delivery vehicle for treatment of aggressiveperiodontitis

用于治疗侵袭性牙周炎的受控抗生素递送载体

• 批准号: 10662640
• 负责人: Angela C. Brown
• 金额: $ 21.64万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662640
• 关键词: Actinobacillus actinomycetemcomitans; Adolescent; Adsorption; Affect; Affinity; Antibiotic Resistance; Antibiotics; Automobile Driving; Bacteria; Binding; Cell Survival; Cell membrane; Cells; Cholesterol; Clinical; Clinical Treatment; Coculture Techniques; Development; Disease; Disease Progression; Encapsulated; Engineering; Equus caballus; Future; Goals; Gram-Negative Bacteria; Immune; Infection; Left; Lipids; Liposomes; Mediating; Membrane; Membrane Lipids; Mission; Modality; Modeling; National Institute of Dental and Craniofacial Research; Oral health; Outcome; Pathogenesis; Pathogenicity; Patients; Periodontal Infection; Periodontitis; Phase; Plasma Cells; Porifera; Proteins; Recommendation; Research; Role; System; Testing; Therapeutic; Toxin; Virulence Factors; Work; adolescent patient; adverse drug reaction; biophysical analysis; common treatment; delivery vehicle; host colonization; improved; innovation; leukotoxin; liposomal delivery; nanomolar; novel; novel therapeutics; phase change; scaling and root planing; therapeutic target; treatment strategy

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.

项目总结/文摘