Photodynamic therapy of oral candidiasis

描述（由申请人提供）： 真菌白色念珠菌通常定植于身体的上皮表面，消化道被认为是定植的主要部位。口咽念珠菌病（OPC）是由于真菌过度生长和渗透口腔上皮时，身体的物理和免疫防御以某种方式受到损害。OPC常见于艾滋病和糖尿病。疾病或药物治疗导致的唾液腺功能受损与OPC的高发病率相关。C.生长粘膜表面上的白色念珠菌作为生物膜导致抗真菌治疗缺乏成功性并导致复发性感染。因此，需要新的治疗方法来预防和治疗OPC。初步研究表明光动力疗法（PDT）对C。使用临床批准的光敏剂在体外对白色念珠菌进行检测。我们建议继续使用C.白色念珠菌生物膜，并评估PDT在OPC动物模型中的功效。中心假设是，体外形成的白色念珠菌生物膜的PDT的最佳参数的开发可用于告知在实验动物模型中OPC的局部治疗的开发。具体目标1：评估选定的光敏剂在白色念珠菌生物膜的PDT中的功效。路易斯安那州比较所选PDT剂对光照射C.白色念珠菌单层。IB.为了确定光敏剂的吸收，光动力作用的荧光光谱特征和生物体损伤之间的空间关系，在一个C。用激光扫描共聚焦荧光显微镜观察白色念珠菌生物膜。 具体目标2：在动物模型中证明PDT治疗OPC的原理。 2a.研究光敏剂在C.在新鲜切除的组织和活体动物中使用原位荧光成像技术检测白色念珠菌和周围正常组织。 2b.证明PDT治疗C.大鼠口腔内白念珠菌感染的研究

DESCRIPTION (provided by applicant): The fungus Candida albicans commonly colonizes the epithelial surfaces of the body, with the alimentary canal considered as the primary site of colonization. Oropharyngeal candidiasis (OPC) results from fungal overgrowth and penetration of oral epithelium when the body's physical and immunological defenses are compromised in some way. OPC is commonly seen in AIDS and diabetes. Impairment of salivary gland function by disease or medical treatment is correlated with a high incidence of OPC. Growth of C. albicans on mucosal surfaces as a biofilm contributes to the lack of success of antifungal therapy and leads to recurrent infections. Therefore, novel therapeutic approaches are needed to prevent and treat OPC. Preliminary studies demonstrate the efficacy of photodynamic therapy (PDT) against C. albicans in vitro using a clinically approved photosensitizing agent. We propose to continue the in vitro studies using C. albicans biofilms, and evaluate the efficacy of PDT in an animal model of OPC. The central hypothesis is that the development of optimal parameters for PDT of C, albicans biofilms formed in vitro can be used to inform the development of a topical treatment of OPC in an experimental animal model. Specific aim 1: To assess the efficacy of selected photosensitizing agents in PDT of a Candida albicans biofilm. la. To compare the ability of selected PDT agents to photosensitize damage to optically irradiated C. albicans monolayers. Ib. To determine the spatial relationships between photosensitizing agent uptake, fluorescence spectroscopic signatures of photodynamic action, and organism damage in a C. albicans biofilm by laser scanning confocal fluorescence microscopy. Specific aim 2: To demonstrate proof of principle of PDT in the treatment of OPC in an animal model. 2a. To evaluate the distribution and retention of photosensitizing agents in C. albicans and surrounding normal tissue using in situ fluorescence imaging techniques in freshly excised tissue and in living animals. 2b. To demonstrate proof of principle of PDT in the treatment of C. albicans infection in the oral cavity of rats in vivo.