Intravaginal ring microbicide formulations comprising multiple anti-HIV agents

包含多种抗HIV剂的阴道内环杀微生物剂制剂

• 批准号: 7681731
• 负责人: Thomas J. Smith
• 金额: $ 23.68万
• 依托单位: OAK CREST INSTITUTE OF SCIENCE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681731
• 关键词: Acquired Immunodeficiency Syndrome; Africa South of the Sahara; Animal Model; Animals; Anti-HIV Agents; Anti-Inflammatory Agents; Anti-Retroviral Agents; Anti-inflammatory; Antiviral Agents; Cervical; Characteristics; Clinical; Clinical Trials; Contraceptive Agents; Cytomegalovirus Retinitis; Development; Devices; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Economic Development; Epithelium; Eye; FDA approved; Fluocinolone Acetonide; Foundations; Fumarates; GMP lots; Ganciclovir; Gel; Gilead brand of tenofovir disoproxil fumarate; Goals; HIV; HIV Infections; Heterosexuals; Implant; In Vitro; Institutes; Investigational Drugs; Knowledge; Lead; Living Standards; Marketing; Measures; National Institute of Child Health and Human Development; Parents; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I/II Trial; Posterior Uveitis; Process; Prodrugs; Production; Prophylactic treatment; Recording of previous events; Regulatory Pathway; Reporting; Research; Research Personnel; Resistance; Risk; Safety; Sampling; Science; Services; Solubility; Steroids; System; Technology; Tenofovir; Tenofovir disoproxil fumarate; Testing; United States National Institutes of Health; Vagina; Vaginal Ring; Woman; Work; absorption; aqueous; base; drug distribution; empowered; high risk; implantation; improved; in vitro testing; in vivo; innovation; microbicide; multiple drug use; non-nucleoside reverse transcriptase inhibitors; novel; pinacolyl methylphosphonic acid; programs; sex; vaginal fluid

DESCRIPTION (provided by applicant): The broad long term goal of this project is to empower women to protect themselves from HIV infection through the development of improved microbicides based on our clinically proven sustained release technology platform. Using this platform drug delivery devices for a broad range of drugs have been approved by the FDA and are in current clinical use. The ganciclovir intraocular implant: the Vitrasert(r), approved for the treatment of AIDS related CMV retinitis releases the relatively soluble antiviral ganciclovir into the eye for a period of eight months. The Retisert(r) releases the relatively insoluble steroid fluocinolone acetonide for up to three years. We propose to utilize this platform to develop sustained release vaginal ring microbicide formulations for the antiretroviral agents tenofovir and TMC 120. In the first two years of this project (R21) we will evaluate the hypothesis that, when incorporated into a ring formulation, the prodrug tenofovir disoproxil fumarate is superior to the parent drug tenofovir as candidate microbicide. In the second phase of the project (R33) we will manufacture and test ring formulations containing multiple antiviral agents. We hypothesize that, using our unique drug delivery platform, there will be no loss of elution characteristics with the incorporation of multiple drugs into our system. The successful completion of this project will result in the submission of an investigational new drug exemption (IND) leading to clinical trials for these formulations. Each day 15,000 people are infected by HIV, the majority in sub-Saharan Africa and a growing percentage women infected though heterosexual sex. The broad long term goal of this project is to empower women to protect themselves from HIV infection through the development of improved vaginal ring formulations for microbicides based on the sustained release drug delivery of antiviral agents. Our clinically proven sustained release drug delivery platform uniquely allows us to deliver drug of both high and low aqueous solubility. We propose to utilize this platform technology to develop long-term vaginal ring formulations for the potential microbicides tenofovir and TMC-120.

描述（由申请人提供）：该项目的广泛长期目标是通过基于我们临床证明的持续释放技术平台来开发改进的菌心，以赋予妇女保护自己免受艾滋病毒感染的能力。 FDA已批准使用此平台药物输送设备来进行广泛的药物，并且正在使用当前的临床用途。 Ganciclovir的眼内植入物：批准用于治疗与AIDS相关的CMV视网膜炎的Vitrasert（R）将相对可溶的抗病毒Ganciclovir释放到眼睛中八个月。 retisert（R）释放了相对不溶性的类固醇乙醇乙醇乙烯剂长达三年。我们建议利用这个平台为抗逆转录病毒药物替诺福韦和TMC 120开发持续释放的阴道环菌苷制剂。在该项目的前两年（R21），我们将评估以下假说，即当将其纳入环形替代性替代性替代性牛皮化型药物中时，将其纳入环形表述中时，将其纳入partiactic candofir candofir。在项目的第二阶段（R33）中，我们将制造和测试环制剂包含多种抗病毒剂。我们假设，使用我们独特的药物输送平台，将多种药物纳入我们的系统不会失去洗脱特性。该项目的成功完成将导致提交研究性新药豁免（IND），从而为这些配方进行临床试验。每天有15,000人感染艾滋病毒，大多数在撒哈拉以南非洲和越来越多的妇女感染了异性恋性。该项目的长期长期目标是通过基于持续释放药物的抗病毒药物递送来改善杀菌剂的阴道配方来保护自己免受艾滋病毒感染的影响。我们临床证明的持续释放药物输送平台独特地使我们能够提供高和低水溶性的药物。我们建议利用这种平台技术为潜在的微生物Tenofovir和TMC-1220开发长期阴道表配方。

项目成果

Pharmacokinetics of a multipurpose pod-intravaginal ring simultaneously delivering five drugs in an ovine model.

多用途荚阴道环在绵羊模型中同时输送五种药物的药代动力学。

• DOI: 10.1128/aac.00547-13
• 发表时间: 2013
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Moss,JohnA;Malone,AmandaM;Smith,ThomasJ;Kennedy,Sean;Nguyen,Cali;Vincent,KathleenL;Motamedi,Massoud;Baum,MarcM
• 通讯作者: Baum,MarcM

Tenofovir and tenofovir disoproxil fumarate pharmacokinetics from intravaginal rings.

• DOI: 10.1097/qad.0b013e3283509abb
• 发表时间: 2012-03-27
• 期刊: AIDS (London, England)
• 作者: Moss JA;Baum MM;Malone AM;Kennedy S;Kopin E;Nguyen C;Gilman J;Butkyavichene I;Willis RA;Vincent KL;Motamedi M;Smith TJ
• 通讯作者: Smith TJ