Intra-oral Drug Delivery Systems for HIV/AIDS Patients

HIV/艾滋病患者的口腔内给药系统

• 批准号: 6938529
• 负责人: SID KALACHANDRA
• 金额: $ 37.98万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-20 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938529
• 关键词: HIV infections; acyclovir; adult human (21+); bacterial disease; chlorhexidine; clinical biomedical equipment; clinical research; clinical trials; combination chemotherapy; copolymer; drug delivery systems; ganciclovir; gastrointestinal infection; human subject; human therapy evaluation; local antiinfective agents; microorganism disease chemotherapy; mouth; mycosis; nystatin; opportunistic infections; oral administration; patient oriented research; pharmacology; slow release drug; technology /technique development; topical drug application; virus diseases

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.

目前，尚无有效的口服输送系统可以长时间在治疗水平上连续释放药物，以治疗免疫功能低下的患者中细菌，真菌或病毒感染。我们预计，将药物直接送到感染部位将是有效的，并且会忽略对这些疾病的全身治疗的必要性，从而避免了全身给药观察到的副作用。该提出的项目是开发改进的生物相容性聚合设备。这些设备应提供治疗剂的连续内释放，包括目前用于治疗患有口服白色念珠菌和病毒感染的患者，包括抗菌，抗真菌药和抗病毒药药。拟议的研究集中于 优化FDA批准的聚合物乙烯乙烯乙烯乙二醇（EVA）共聚物的药物输送特性，作为一种口腔防护装置，可持续释放当前FDA批准的治疗剂，单独或单独或组合组合。释放药物的功效将以从EVA或其他基于生物相容性的聚合物设备释放为测量。根据体外研究的结果，将通过安全的药物浸渍的口腔检查安全和功效进行临床试验。测试的假设是，从治疗水平上从聚合物装置中抗菌剂的内部连续释放将有效减轻导致口腔感染的病原体的口服负担。基于体外研究的结果，上升 将进行剂量试验以确定安全性，药物递送和生物避免性。治疗药物治疗口腔疾病患者的牙周疾病和疱疹病变的临床功效将针对对照组进行评估。将对口腔疾病患者的牙周疾病状况和疱疹病变的改善进行评估。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中，将评估药物对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种新的新型程序，用于使用实验室延长的局部药物递送的新程序 牙医很容易获得的方法和材料。有效而有效的受控药物释放设备可能在免疫功能低下的患者中具有广泛的治疗应用。