Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides.
Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides.
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DOI：
10.1002/jps.23913
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发表时间：
2014-05
影响因子：
3.8
通讯作者：
Malcolm, R. Karl
中科院分区：
文献类型：
--
作者：
Forbes, Claire J.;Mccoy, Clare F.;Murphy, Diarmaid J.;Woolfson, A. David;Moore, John P.;Evans, Abbey;Shattock, Robin J.;Malcolm, R. Karl
关键词：
我们先前报道了用于持续阴道给药的CCR 5靶向进入抑制剂马拉韦罗的非水硅酮弹性体凝胶（SEG）。在这里，我们描述了化学改性的SEG（h-SEG），其中疏水性的环聚甲基硅氧烷组分部分地被相对亲水性的硅烷醇封端的聚二甲基硅氧烷（st-PDMS）取代。马拉韦罗和恩曲他滨（一种核苷逆转录酶抑制剂），目前正在评估作为局部杀微生物剂，以对抗人类免疫缺陷病毒1型（HIV-1）的性传播，被用作抗逆转录病毒（ARV）的模型药物。h-SEGs中st-PDMS分子量和浓度显著影响凝胶粘度和ARV体外释放。出乎意料的是，用较低分子量等级的st-PDMS制备的凝胶显示出较高的粘度。与水性羟乙基纤维素（HEC）凝胶相比，h-SEG在24小时内提供增强的释放，不改变模拟阴道液（SVF）的pH，并且显示出比标准羟乙基纤维素（HEC）阴道凝胶更少的细胞毒性。ARV溶解度随着st-PDMS分子量的降低而增加（即随着羟基含量百分比的增加），这有助于解释体外释放趋势。染料渗入和SVF稀释研究证实了h-SEG的亲水性增加。h-SEG具有用于阴道药物递送的潜力，特别是用于基于ARV的HIV-1杀微生物剂。
We previously reported non-aqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc. Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). Maraviroc and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard hydroxyethylcellulose (HEC) vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e. as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides.
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DOI：
10.1097/qad.0b013e32834541d9
发表时间：
2011-04-24
期刊：
AIDS (London, England)
影响因子：
--
作者：
Abdool Karim SS;Richardson BA;Ramjee G;Hoffman IF;Chirenje ZM;Taha T;Kapina M;Maslankowski L;Coletti A;Profy A;Moench TR;Piwowar-Manning E;Mâsse B;Hillier SL;Soto-Torres L;HIV Prevention Trials Network (HPTN) 035 Study Team
通讯作者：
HIV Prevention Trials Network (HPTN) 035 Study Team
影响因子：
56.3
作者：
Cutler, Blayne;Justman, Jessica
通讯作者：
Justman, Jessica
影响因子：
6.2
作者：
Andrews, Gavin P.;Donnelly, Louise;Jones, David S.;Curran, Rhonda M.;Morrow, Ryan J.;Woolfson, A. David;Malcolm, R. Karl
通讯作者：
Malcolm, R. Karl
影响因子：
4.9
作者：
Haaland, Richard E.;Evans-Strickfaden, Tammy;Hart, Clyde E.
通讯作者：
Hart, Clyde E.
影响因子：
5.8
作者：
Chatterton, BE;Penglis, S;Hunt, B
通讯作者：
Hunt, B