TARGETED DRUG DELIVERY SYSTEM FROM RSV

呼吸道合胞病毒(RSV)的反复感染根本就没有发生 年龄。然而，它们在婴幼儿中尤其令人担忧。 呼吸道合胞病毒是导致严重、急性下限的最常见原因的儿童 呼吸道感染。呼吸道合胞病毒是毛细支气管炎的主要原因 在婴儿期和儿童时期肺炎的主要原因之一。 推荐雾化吸入治疗严重呼吸道合胞病毒感染 利巴韦林的临床疗效微乎其微。我们提议写一部小说 呼吸道合胞病毒感染的治疗理念。人造病毒包膜 含有抗病毒药物的(病毒体)将以这样的方式配制 以呼吸道细胞摄取为目标的方式。病毒体将会是 由RSV G(附着)和F(融合)表面构成 糖蛋白。其目的是模仿所采用的分子策略 通过呼吸道合胞病毒附着和穿透肺内的上皮细胞(活跃) 靶向)以及为牙槽提供强烈的刺激 巨噬细胞吞噬含药小泡(被动 目标)。其目标是积累治疗浓度的 在RSV的两个主要宿主细胞内选择性地使用抗病毒药物 呼吸道上皮细胞和肺泡巨噬细胞。 具体目标是： 1.确定RSV病毒小体的最佳组成，以获得最大和 与宿主细胞快速融合。2.测定利巴韦林的能力- 负载病毒小体抑制呼吸道合胞病毒在Hep-2细胞和肺泡中的复制 巨噬细胞与游离利巴韦林的比较。3.评估的稳定性 这些病毒小体在雾化和溶叶化的基础上。4.评估 利巴韦林病毒小体的毒性表现在：a) 肺泡巨噬细胞活性和吞噬功能；b)改变 上皮细胞形态和睫毛功能；c) 羔羊的呼吸道功能；d)诱导呼吸道合胞病毒致敏 羔羊体内的F或G糖蛋白；以及e)呼吸道功能的改变 在健康的成年志愿者中。5.比较利巴韦林的疗效- 载病毒小体与游离利巴韦林联合治疗低血压病 雏羊呼吸道合胞病毒感染引起的呼吸道疾病 评估这种治疗性干预措施对再暴露于 病毒。

Recurrent infections with respiratory syncytial virus (RSV) occur at all ages. However, they are of particular concern in infants and young children where RSV is the most common cause of severe, acute lower respiratory tract infections. RSV is the major cause of bronchiolitis during infancy and one of the major causes of pneumonia in childhood. The recommended treatment of severe RSV infection, aerosolized ribavirin, has only minimal clinical efficacy. We propose a novel concept for the therapy of RSV infections. Artificial viral envelopes (virosomes) containing an antiviral drug will be formulated in such a manner as to target for respiratory cell uptake. Virosomes will be constructed with RSV G (attachment) and F (fusion) surface glycoproteins. The objective is to mimic the molecular strategy adopted by RSV to attach and penetrate epithelial cells in the lung (active targeting) as well as to provide a strong stimulus for alveolar macrophages to phagocytize the drug-containing vesicle (passive targeting). The goal is to accumulate therapeutic concentrations of antiviral drug selectively within the two major host cells for RSV, the respiratory epithelial cell and the alveolar macrophage. The specific aims are: 1. To determine the optimal composition of RSV virosomes for maximum and rapid fusion with host cells. 2. To measure the ability of ribavirin- loaded virosomes to inhibit RSV replication in HEp-2 cells and alveolar macrophages compared to free ribavirin. 3. To assess the stability of these virosomes upon nebulization and lyophylization. 4. To assess toxicity of ribavirin-loaded virosomes in terms of: a) alterations in alveolar macrophage viability and phagocytic function; b) alterations in epithelial cell morphology and ciliary function; c) alterations in airway function in the lamb; d) induction of airway sensitization to RSV F or G glycoprotein in the lamb; and e) alterations in airway function in healthy adult volunteers. 5. To compare the efficacy of ribavirin- loaded virosomes with free ribavirin for the treatment of lower respiratory tract disease induced by RSV infection in young lambs and to evaluate the effects of this therapeutic intervention on reexposure to the virus.