Intra-oral Drug Delivery Systems for HIV/AIDS Patients

目前，没有有效的口服递送系统，其将在治疗水平下持续释放药物以治疗免疫功能低下患者的细菌、真菌或病毒感染。我们预期，将药物直接局部递送至感染部位将是有效的，并且将省略对这些病症的全身治疗的需要，从而避免在全身施用时观察到的副作用。本拟议项目旨在开发改进的生物相容性聚合物器械。这些装置应该提供治疗剂的连续口内释放，所述治疗剂包括目前用于治疗患有口腔疾病（例如，白色念珠菌和艾滋病患者中的病毒感染）的患者的抗微生物、抗真菌和抗病毒药。拟议的研究重点是 优化FDA批准的聚合物材料，乙烯-乙酸乙烯酯（伊娃）共聚物的药物递送特性，其作为用于持续释放当前FDA批准的治疗剂，氯己定、制霉菌素、更昔洛韦和阿昔洛韦（单独或组合）的护齿装置。释放的药物的效力将被测量为从伊娃或其他生物相容性聚合物基器械释放。基于体外研究的结果，将使用定制的药物浸渍护齿器进行临床试验，测试安全性和有效性。待检验的假设是，在治疗水平下，聚合物器械的口内持续释放抗菌剂将有效降低引起口腔感染的病原体的口腔负荷。根据体外研究的结果， 将进行剂量试验以确定安全性、药物递送和生物利用度。将相对于对照评价治疗剂治疗口腔疾病患者的牙周疾病和疱疹病变的临床功效。将对照组评价口腔疾病患者牙周病状态和疱疹病变的改善情况。将在我们的口腔微生物学诊断设施（CLIA认证）和口腔病毒学实验室评估药物对药物治疗艾滋病患者牙菌斑和唾液样本中细菌病原体水平的影响。这些拟议的研究将建立一个新的和新颖的程序的基础上，持续局部药物输送超过延长的时间段，使用实验室 方法和材料是牙医容易获得的。这种有效的药物控释装置在免疫功能低下的患者中具有广泛的治疗应用。

At present, there are no effective oral delivery systems that will release drugs continuously at therapeutic levels for extended periods to treat bacterial, fungal or viral infections in immunocompromised patients. We expect that direct local delivery of drugs to the infected sites will be efficacious and will omit the need for systemic treatment of these conditions, thereby avoiding side effects that are observed with systemic administration. This proposed project is to develop improved biocompatible polymeric devices. These devices should provide a continuous intraoral release of therapeutic agents including antimicrobial, antifungal and antiviral drugs currently being used in the treatment of patients suffering from oral conditions such as Candida albicans and viral infections in AIDS patients. The proposed studies are focused on optimizing the drug delivery characteristics of an FDA approved polymeric material, ethylene vinyl acetate (EVA) copolymer as a mouth guard device for sustained release of current FDA approved therapeutic agents, chlorhexidine, nystatin, ganciclovir and acyclovir, alone or in combination. The efficacies of the released drugs will be measured as released from the EVA or other biocompatible polymer based devices. Based on the results of in vitro studies, clinical trials will be performed with customized drug-impregnated mouth guards testing safely and efficacy. The hypothesis to be testedis that the intra-oral continuous release of antimicrobial agents from polymeric devices at therapeutic levels will be effective in decreasing the oral burden of pathogens causing oral infections. Based on the results of in vitro studies, an ascending dose trial will be performed to determine safety, drug delivery, and bioavaUability. Clinical efficacy of the therapeutic agents to treat periodontal diseases and herpetic lesions in patients with oral disease will be evaluated against controls. Improvements of periodontal disease status and herpetic lesions in patients with oral disease will be evaluated against controls. Effects of drugs on levels of bacterial pathogens in plaque and saliva samples from drug-treated AIDS patients will be assessed in our oral microbiology diagnostic facility (CLIA-certified) and in a laboratory of oral virology. These proposed studies will establish the basis for a new and novel procedure for sustained local drug delivery over extended time periods using laboratory methods and materials that are readily available to dentists. The effective and efficient controlled drug release devices could have broad therapeutic applications in immunocompromised patients.