Thermostable vaginal probiotic microbicide

描述(由申请人提供)：最近修订的统计数据显示，全球艾滋病毒携带者人数超过3300万，其中68%在撒哈拉以南非洲。目前的艾滋病毒预防方法，如使用避孕套、一夫一妻制和禁欲，并不总是可行的。仍然迫切需要改进艾滋病毒预防技术。局部杀微生物剂的发展代表了防止性传播疾病的一个新的令人兴奋的领域。其中，应用活的益生菌杀菌剂(PBM)是一种很有前途的预防方法。我们的最终目标是开发高效、优化、多菌种、耐热性和易于释放的益生菌阴道局部杀菌剂。为了实现这一目标，我们将稳定阴道益生菌，以便在环境温度较高的情况下长期储存，并在快速溶解薄膜制造所需的温度(60℃及以上)下短期存活。这项建议的基石是：1)蒸发保存“(PBV)--一种在高温下干燥稳定益生菌和其他脆弱生物制品的创新、正在申请专利的方法，以及2)正在优化的快速溶解薄膜技术，以提供传统的阴道杀菌剂。该策略可以简单地描述为，占据阴道上皮并提供针对HIV、BV和STI的持久保护环境。含有PBV阴道益生菌的小(10-50？m)玻璃糖颗粒将被配制成利用水溶性聚合物碱的薄膜。薄膜提供了一个独特的给药平台，与其他剂型相比具有许多优势。在最近的一项研究中，比较了女性对电影、片剂和胚珠的偏好，结果表明，在被研究的女性中，薄膜剂型的接受度最高。我们认为，与其他可能的益生菌杀菌剂输送方法相比，女性更喜欢使用阴道膜，特别是如果定植于阴道上皮的细菌的长效作用允许较少使用的话。PBM在常温下长期储存后，将使用阴道和宫颈上皮细胞培养模型来表征其生物学特性。 与公共卫生有关：艾滋病毒携带者人数持续增加，该流行病正在女性化。2007年底，妇女占全世界艾滋病毒携带者成人的50%，在撒哈拉以南非洲占61%。在新的艾滋病毒病例中，至少有一半是25岁以下的人，而在13-19岁的人中，54%是少女。因此，迫切需要开发一种有效的女性控制杀微生物剂产品，以防止感染艾滋病毒。阴道固有的菌群为感染提供了一种天然的防御屏障，因此益生菌杀菌剂为预防提供了一种有前途的策略。该项目旨在评估一种策略，以克服其成功应用的两个障碍，即在相关环境条件下的长期细菌保存和用户可接受的稳定的阴道给药系统。汽化保存和薄膜剂型与多菌种配方的创新结合提供了一种独特的技术，可以克服现有障碍，提供安全有效的益生菌杀菌剂产品，以保护妇女免受艾滋病毒感染。

DESCRIPTION (provided by applicant): Recently revised statistics show the number of individuals living with HIV at over 33 million worldwide, with 68% being in sub-Saharan Africa. Current HIV prevention methods, such as condom use, monogamy and abstinence, are not always feasible. The need for improved HIV preventative technologies remains urgent. The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases. Of these, application of live probiotic bacterial microbicides (PBM) represents a promising preventative method. Our ultimate goal is to develop potent optimized multistrain thermostable and easily deliverable probiotic vaginal topical microbicides. To achieve this goal we will stabilize vaginal probiotics for long-term storage at high ambient temperatures and short term survival at temperatures required for quick dissolve film manufacturing (60¿C and above). The cornerstones of this proposal are: 1) Preservation by Vaporization" (PBV) - an innovative, patent pending method of dry-stabilizing probiotics bacteria and other fragile biologicals at high ambient temperatures, and 2) Quick-dissolve thin film technology that is being optimized to deliver conventional vaginal microbicides. The strategy can be described briefly as, to occupy the vaginal epithelium and provide a long lasting protective environment against HIV, BV, and STI acquisition small (10-50 ¿m) glassy sugar particles containing PBV vaginal probiotic bacteria will be formulated into thin films which utilize a water soluble polymer base. Thin films offer a unique delivery platform which has a number of advantages over other dosage forms. In a recent study comparing women's preference between films, tablets and ovules, the film dosage form was shown to have greatest acceptability among women studied. We believe that women will prefer using a vaginal film over other potential methods of probiotic microbicide delivery especially if a long-acting effect of the bacteria colonizing vaginal epithelium allows for less frequent use. Biologic properties of PBM after long-term storage at ambient temperatures will be characterized using cell culture models of vaginal and cervical epithelium. PUBLIC HEALTH RELEVANCE: As the number of individuals living with HIV continues to rise and a feminization of the epidemic is occurring. At the end of 2007 women accounted for 50% of all adults living with HIV worldwide and 61% in sub-Saharan Africa. Of new HIV cases at least half are in individuals less than 25 years of age and of those aged 13-19 54% are teenage girls. For this reason there is a desperate need for the development of an effective female controlled microbicide product to protect against acquisition of HIV. The innate vaginal flora provide a natural defensive barrier to infection hence a probiotic microbicide provides a promising strategy for prevention. This project serves to evaluate a strategy to overcome two barriers to its successful application, long term bacterial preservation at relevant environmental conditions and a user acceptable stable delivery system for vaginal administration. The innovative combination of preservation by vaporization and thin film dosage forms with use of multi-strain formulations provides a unique technology which can serve to overcome existing barriers to provide a safe and effective probiotic microbicide product to protect women from acquisition of HIV.