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: 6459475
• 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 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6459475
• 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.

这个创新研究项目的目标是开发简单的 用于口内递送抗微生物剂的双功能分子。的 双功能杂合分子将各自由载体序列组成 对牙齿和薄膜表面具有高亲和力， 抗菌肽这两个序列将通过 生物降解键有了这种连接，抗菌序列固有地 将从牙齿表面有效地释放 在唾液中通过口腔生理和微生物环境， 控制和持续释放抗微生物剂，从而提供 一种新颖而有效的口腔内给药方法。本研究项目 包括：1）通过合理选择载体合成杂化分子 来自唾液抑癌素的序列和来自杆菌素的抗菌序列 2）测定杂交分子的毒性，以确保 它们仅对微生物具有细胞毒性; 3）描述整体的作用 唾液对杂化分子稳定性的影响; 4）评估吸附 杂化分子在羟基磷灰石上的脱附特性 表面; 5）测定白色念珠菌的粘附程度， 牙龈卟啉单胞菌、伴放线放线杆菌、链球菌 变形链球菌、戈登链球菌和血链球菌的杂交体上 吸附羟基磷灰石表面。这项拟议的研究将确定新的， 安全，负担得起的混合分子，用于预防和治疗 与牙菌斑有关的口腔疾病。该杂化分子可以直接用作 局部冲洗，或冲洗剂，或者它们可以专业地应用于 龈下区域。口腔生理和微生物环境将 自然诱导抗菌肽的解离和释放 从牙齿表面进入口腔感染部位。杂交分子 将作为一个有效的本地药物输送系统，并消除 与现有的局部递送相关的不适和保留问题 装置.该杂合分子将具有很高的临床应用潜力， 作为抗牙斑剂的商业应用。