Thermostable vaginal probiotic microbicide

耐热阴道益生菌杀菌剂

• 批准号: 8111036
• 负责人: Victor Bronshtein
• 金额: $ 33.28万
• 依托单位: UNIVERSAL STABILIZATION TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111036
• 关键词: AIDS prevention; Abstinence; Accounting; Acids; Adolescence; Adult; Africa South of the Sahara; Age-Years; Anaerobic Bacteria; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antiviral Agents; Bacteria; Bacterial Vaginosis; Biological; Biological Preservation; Cell Culture Techniques; Cells; Cervical; Clinical Research; Coitus; Cold Chains; Contracts; Development; Dosage Forms; Drug Formulations; Environment; Epidemic; Epithelium; Female; Feminization; Film; Freeze Drying; Goals; HIV; Individual; Infection; Intestines; Intravaginal Administration; Lactobacillus; Legal patent; Life; Local Microbicides; Mechanics; Methods; Modeling; National Institute of Allergy and Infectious Disease; Phase; Polymers; Powder dose form; Preparation; Prevention; Prevention strategy; Primates; Probability; Probiotics; Procedures; Production; Property; Recovery; Research Infrastructure; Risk; Sexually Transmitted Diseases; Suppositories; System; Tablets; Techniques; Technology; Temperature; Therapeutic; Time; Universities; Vagina; Washington; Water; Woman; aged; base; cold temperature; condoms; girls; improved; innovation; man; microbicide; particle; preference; prototype; safety testing; statistics; sugar; transmission process; user-friendly; vaginal microbicide; vaporization

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.

描述（由适用提供）：最近修订的统计数据显示，全世界有超过3300万名艾滋病毒的人数，有68％在撒哈拉以南非洲。当前的艾滋病毒预防方法，例如使用避孕套，一夫一妻制和禁欲，并不总是可行的。需要改善HIV预防技术的需求仍然是紧迫的。局部微生物的发展代表了预防性传播疾病的一个新的令人兴奋的领域。其中，实时益生菌杀菌剂（PBM）的应用代表了一种有希望的预防方法。我们的最终目标是开发潜在的优化多层铅热稳定性且易于可释放的益生菌阴道局部局部杀菌剂。为了实现这一目标，我们将稳定阴道益生菌，以在高环境温度下长期存储，并在快速溶解膜制造（60“及以上）所需的温度下短期存活。该提议的基石是：1）（PBV） - 一种创新的，专利的待处理方法，用于使益生菌细菌和其他脆弱的生物制剂在高环境温度下以及其他脆弱的生物制剂，以及2）2）快速分解薄膜技术，可提供最优化的传统的薄膜，以提供常规的阴道型和策略。针对HIV，BV和STI采集，将含有PBV的玻璃糖颗粒含有阴道益生菌细菌，将其配制为薄膜，使用固体聚合物底部的薄膜，提供了与其他剂量相比，在其他剂型中，有许多优势。在研究女性中，我们认为女性会喜欢使用阴道膜，而不是其他潜在的益生菌杀菌剂递送方法，特别是如果细菌殖民的阴道上皮的长效作用允许使用较少的使用。长期存储在环境温度下的生物学特性将使用阴道和宫颈上皮的细胞培养模型来表征。 公共卫生相关性：随着艾滋病毒携带者的人数继续增加，流行病的女性化正在发生。在2007年底，妇女占全世界享有艾滋病毒的所有成年人的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岁以下的个体，而年龄在13-19岁的人中，有少年女孩。因此，迫切需要开发有效的女性受控杀伤力产品来防止收购艾滋病毒。先天的阴道菌群为感染提供了自然的防御障碍，因此益生菌杀菌剂为预防提供了有希望的策略。该项目旨在评估一项策略，以克服其成功应用的两个障碍，在相关环境条件下保存长期细菌，以及用户可接受的稳定输送系统来进行阴道给药。通过使用多晶体配方，通过分散和薄膜剂型保存的创新组合提供了一种独特的技术，可以克服现有的障碍，以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的收购。