Thermostable vaginal probiotic microbicide

描述（由申请人提供）：最近修订的统计数据显示，全球艾滋病毒感染者人数超过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。改进艾滋病毒预防技术的需求仍然迫切。局部杀微生物剂的发展代表了预防性传播疾病的一个新的和令人兴奋的领域。其中，应用活益生菌杀菌剂（PBM）是一种很有前途的预防方法。我们的最终目标是开发有效的优化多菌株耐热性和易于输送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，使其在高温环境下长期储存，在快速溶解薄膜制造所需的温度（60℃及以上）下短期存活。该提案的基础是：1)“蒸发保存”（PBV）——一种在高温环境下干燥稳定益生菌和其他脆弱生物制剂的创新专利方法，以及2)快速溶解薄膜技术，该技术正在优化，用于输送传统的阴道杀微生物剂。该策略可以简单地描述为，占领阴道上皮，并提供一个长期的保护环境，以防止HIV， BV和STI获取小（10-50¿m）玻璃糖颗粒含有PBV阴道益生菌将配制成薄膜，利用水溶性聚合物基础。薄膜提供了一种独特的递送平台，与其他剂型相比具有许多优点。在最近的一项研究中，比较了女性对胶片、片剂和胚珠的偏好，胶片剂型在被研究的女性中被证明是最容易接受的。我们相信女性会更喜欢使用阴道膜，而不是其他潜在的益生菌杀微生物剂输送方法，特别是如果细菌定殖阴道上皮的长效效果允许较少使用。PBM在室温下长期储存后的生物学特性将通过阴道和宫颈上皮细胞培养模型来表征。

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.