Novel Bifunctional Molecules for Intraoral Drug Delivery

用于口腔内药物输送的新型双功能分子

• 批准号: 6622956
• 负责人: ANTONY R PERIATHAMBY
• 金额: $ 14.5万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622956
• 关键词: SDS polyacrylamide gel electrophoresis; adsorption; antibiotics; clinical research; cytotoxicity; defensins; drug administration routes; drug delivery systems; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; drug vehicle; human subject; hydroxyapatites; nuclear magnetic resonance spectroscopy; oral administration; oral bacteria; phlebotomy; radiotracer; saliva; surface property; synthetic peptide; tooth surface

DESCRIPTION: The goal of this innovative research project is to develop simple bifunctional molecules for intraoral delivery of antimicrobial agents. The bifunctional hybrid molecules will each be composed of a carrier sequence possessing high affinity for tooth and pellicle surfaces, and a natural antimicrobial peptide. These two sequences will be linked to each other with a biodegradable bond. With this linkage, antimicrobial sequences inherently linked to the carrier will be released efficiently from the tooth surface and in saliva through the oral physiological and microbial environment for a controlled and sustained release of the antimicrobial agent, thereby providing a novel and efficient method for intraoral drug delivery. This research project involves: 1) Synthesis of hybrid molecules by rationally selecting carrier sequences from salivary statherin, and antimicrobial sequences from bactenecins and defensins; 2) Determination of toxicity of hybrid molecules to ensure that they are cytotoxic only to microbes; 3) Delineation of the effect of whole saliva on the stability of hybrid molecules; 4) Assessment of the adsorption and desorption characteristics of hybrid molecules onto hydroxyapatite surfaces; 5) Determination of the extent of adherence of Candida albicans, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Streptococcus mutans, Streptococcus gordonii and Streptococcus sanguis onto the hybrid adsorbed hydroxyapatite surfaces. This proposed research will identify new, safe, and affordable hybrid molecules for the prevention and treatment of plaque-related oral diseases. The hybrid molecules can be directly used as a topical rinse, or irrigant or they may be applied professionally to sub-gingival areas. The oral physiological and microbial environment will naturally induce the dissociation and the release of the antimicrobial peptide from the tooth surface into the site of oral infection. The hybrid molecules will serve as an efficient local drug delivery system and eliminate the discomfort and retention problems associated with the existing local delivery devices. The hybrid molecules will have a high potential for clinical and commercial application as anti-plaque agents.

描述：这个创新研究项目的目标是开发简单的

项目成果

Novel molecules for intra-oral delivery of antimicrobials to prevent and treat oral infectious diseases.

用于口腔内递送抗菌剂以预防和治疗口腔传染病的新分子。

• DOI: 10.1042/bj20070810
• 发表时间: 2008
• 期刊: The Biochemical journal
• 作者: Raj,PeriathambyAntony;Rajkumar,Latha;Dentino,AndrewR
• 通讯作者: Dentino,AndrewR