The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention.
The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention.
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DOI：
10.1016/j.antiviral.2015.06.010
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发表时间：
2015-08
影响因子：
7.6
通讯作者：
Buckheit, Robert W., Jr.
中科院分区：
文献类型：
--
作者：
Ham, Anthony S.;Nugent, Sean T.;Peters, Jennifer J.;Katz, David F.;Shelter, Cory M.;Dezzutti, Charlene S.;Boczar, Ashlee D.;Buckheit, Karen W.;Buckheit, Robert W., Jr.
双凝胶™是为安全有效地双腔注射抗逆转录病毒药物而开发的，以减少接受性阴道和肛交期间艾滋病毒传播的高发生率。含有非核苷类逆转录酶抑制剂IQP-0528的双凝胶™S是以经阴道和直肠给药的GRAS辅料制成的。根据可接受的阴道和直肠应用的目标产品简介(™)定义的定量理化和生物学评估，对多凝胶TPP S进行了评估。为了适应安全的直肠给药，根据两种主要的TPP特性，开发了三种双凝胶™制剂(IQB3000、IQB3001和IQB3002)，它们的pH值为6.00，渗透压≤为400mmoL/kg。多凝胶™S在体外无细胞毒性和细菌毒性，在宫颈和结直肠组织中也没有活性损失。由于NNRTI交付减少(减少约65%)，IQB3000被排除在考虑范围之外，而IQB3001由于扩散增加导致泄漏而被删除。含有IQP-0528的IQB3002被定义为我们的先导双凝胶™制剂，具有较强的抗HIV-1活性(EC_(50)=10 nM)。在12个月的稳定性评估中，IQB3002保持了配方的稳定性。这项研究已经确定了一种领先的多凝胶™配方，将安全地提供IQP-0528，以防止艾滋病毒-1在阴道和直肠内的性传播。
The DuoGel™ was developed for safe and effective dual chamber administration of antiretroviral drugs to reduce the high incidence of HIV transmission during receptive vaginal and anal intercourse. The DuoGel™s containing IQP-0528, a non-nucleoside reverse transcriptase inhibitor (NNRTI), were formulated from GRAS excipients approved for vaginal and rectal administration. The DuoGel™s were evaluated based upon quantitative physicochemical and biological evaluations defined by a Target Product Profile (TPP) acceptable for vaginal and rectal application. From the two primary TPP characteristics defined to accommodate safe rectal administration three DuoGel™ formulations (IQB3000, IQB3001, and IQB3002) were developed at pH 6.00 and osmolality ≤ 400 mmol/kg. The DuoGel™s displayed no in vitro cellular or bacterial toxicity and no loss in viability in ectocervical and colorectal tissue. IQB3000 was removed from consideration due to reduced NNRTI delivery (~65% reduction) and IQB3001 was removed due to increase spread resulting in leakage. IQB3002 containing IQP-0528 was defined as our lead DuoGel™ formulation, possessing potent activity against HIV-1 (EC50 = 10 nM). Over 12 month stability evaluations, IQB3002 maintained formulation stability. This study has identified a lead DuoGel™ formulation that will safely deliver IQP-0528 to prevent sexual HIV-1 transmission in the vagina and rectum.
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影响因子：
3.6
作者：
Carballo-Diéguez A;Dolezal C;Bauermeister JA;O'Brien W;Ventuneac A;Mayer K
通讯作者：
Mayer K
影响因子：
3.1
作者：
Carballo-Dieguez, Alex;Exner, Theresa;Mayer, Kenneth H.
通讯作者：
Mayer, Kenneth H.
影响因子：
4.9
作者：
Buckheit, Robert W., Jr.;Hartman, Tracy L.;Cho, Eui-Hwan
通讯作者：
Cho, Eui-Hwan
影响因子：
3.1
作者：
Gorbach PM;Weiss RE;Fuchs E;Jeffries RA;Hezerah M;Brown S;Voskanian A;Robbie E;Anton P;Cranston RD
通讯作者：
Cranston RD
影响因子：
168.9
作者：
Beyrer, Chris;Baral, Stefan D.;van Griensven, Frits;Goodreau, Steven M.;Chariyalertsak, Suwat;Wirtz, Andrea L.;Brookmeyer, Ron
通讯作者：
Brookmeyer, Ron