Intra-oral Drug Delivery Systems for HIV/AIDS Patients

目前，还没有有效的口服给药系统可以在较长时间内以治疗水平持续释放药物来治疗免疫功能低下患者的细菌、真菌或病毒感染。我们预计，将药物直接局部输送到受感染部位将是有效的，并将省去对这些疾病进行系统治疗的需要，从而避免系统给药所观察到的副作用。这项提议的项目是开发改进的生物相容性聚合物装置。这些设备应提供持续的口腔内释放治疗药物，包括目前用于治疗患有白色念珠菌和艾滋病病毒感染等口腔疾病的患者的抗微生物、抗真菌和抗病毒药物。建议的研究主要集中在 优化FDA批准的聚合物材料的药物输送特性，乙烯-乙酸乙烯酯(EVA)共聚物作为口腔保护装置，单独或联合用于当前FDA批准的治疗剂氯己定、制霉菌素、更昔洛韦和阿昔洛韦的缓释。释放的药物的有效性将在从EVA或其他生物兼容聚合物设备中释放时进行测量。根据体外研究的结果，将使用定制的药物浸渍护口器进行临床试验，以测试安全性和有效性。需要检验的假设是，在治疗水平上，从聚合物设备中连续口腔内释放抗菌剂将有效地减少引起口腔感染的病原体的口腔负担。基于体外研究的结果，一个上升的 将进行剂量试验，以确定安全性、药物释放和生物利用度。治疗口腔疾病患者的牙周病和疱疹病变的临床疗效将与对照组进行比较。口腔疾病患者的牙周病状况和疱疹病变的改善情况将与对照组进行评估。药物对接受药物治疗的艾滋病患者的菌斑和唾液样本中细菌病原体水平的影响将在我们的口腔微生物诊断设施(CLIA认证)和口腔病毒学实验室进行评估。这些拟议的研究将为利用实验室在较长时间内持续局部给药的新的新程序奠定基础 牙科医生容易获得的方法和材料。有效、高效的药物控释装置在免疫功能低下患者的治疗中具有广阔的应用前景。

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.