Novel Bifunctional Molecules for Intraoral Drug Delivery

用于口腔内药物输送的新型双功能分子

基本信息

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
项目类别：
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

项目摘要

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双功能分子用于抗菌剂的口腔内递送。这双功能混合分子将分别由载体序列组成对牙齿和颗粒表面具有高亲和力，并且是自然的抗菌肽。这两个序列将与可生物降解键。使用这种联系，抗菌序列固有地与载体相关的链接将有效地从牙齿表面释放通过口服生理和微生物环境在唾液中抗菌剂的控制和持续释放，从而提供一种新颖有效的口腔药物输送方法。这个研究项目涉及：1）合理选择载体合成杂化分子唾液statherin的序列和bactenecins的抗菌序列和防御素； 2）确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）整体效果的描述唾液关于杂交分子的稳定性； 4）评估吸附混合分子在羟基磷灰石上的解吸特性表面； 5）确定白色念珠菌的依从性程度，牙龈卟啉单胞菌，放线杆菌放线菌，链球菌链球菌杂种，gordonii链球菌和链球菌在杂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且负担得起的混合动力分子，以预防和处理与牙菌有关的口腔疾病。混合分子可以直接用作局部冲洗或灌溉剂，或者可以专业地应用于亚地区。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。杂化分子将充当有效的当地药物输送系统，并消除与现有本地交付相关的不适和保留问题设备。混合分子在临床和商业应用为抗扁平药。