Novel Bifunctional Molecules for Intraoral Drug Delivery

描述：这一创新研究项目的目标是开发简单的 用于口腔内给药的双功能分子。这个 每个双功能杂化分子将由一个载体序列组成 对牙齿和膜表面具有高亲和力，天然的 抗菌肽。这两个序列将通过 可生物降解的粘合剂。有了这种联系，抗菌序列固有地 连接到载体上的部分将有效地从齿面释放并 在唾液中通过口腔生理和微生物环境 抗菌剂的受控和持续释放，从而提供 一种新颖高效的口腔给药方法。这项研究项目 包括：1)通过合理选择载体合成杂化分子 来自唾液他汀类的序列和来自杆菌素的抗菌序列 和防御素；2)杂化分子毒性的测定，以确保 它们只对微生物有细胞毒性；3)整体作用的描绘 唾液对杂化分子稳定性的影响；4)吸附性能的评价 杂化分子在羟基磷灰石上的解吸特性 表面；5)白色念珠菌黏附程度的测定， 牙龈卟啉单胞菌、伴生放线杆菌、链球菌 变形杆菌、戈登链球菌和血链球菌在杂交种上 吸附的羟基磷灰石表面。这项拟议的研究将确定新的、 安全、实惠的杂化分子用于预防和治疗 与菌斑相关的口腔疾病。杂化分子可直接用作 局部冲洗，或冲洗剂，也可以专业地应用于 牙龈下区域。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。杂化分子 将作为一种高效的本地药物输送系统，并消除 与现有本地分娩相关的不适和滞留问题 设备。这种杂化分子将具有很高的临床和应用潜力 作为抗菌斑剂的商业应用。

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.