Ramanathan R, Jiang Y, Read B, Golan-Paz S, Woodrow K A
3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA.
Acta Biomater. 2016 May;36:122-31. doi: 10.1016/j.actbio.2016.02.034. Epub 2016 Mar 3.
Nanocarriers are versatile vehicles for drug delivery, and emerging as platforms to formulate and deliver multiple classes of antiretroviral (ARV) drugs in a single system. Here we describe the fabrication of hydrogel-core and lipid-shell nanoparticles (nanolipogels) for the controlled loading and topical, vaginal delivery of maraviroc (MVC) and tenofovir disoproxil fumarate (TDF), two ARV drugs with different mechanisms of action that are used in the treatment of HIV. The nanolipogel platform was used to successfully formulate MVC and TDF, which produced ARV drug-loaded nanolipogels that were characterized for their physical properties and antiviral activity against HIV-1 BaL in cell culture. We also show that administration of these drug carriers topically to the vaginal mucosa in a murine model leads to antiviral activity against HIV-1 BaL in cervicovaginal lavages. Our results suggest that nanolipogel carriers are promising for the encapsulation and delivery of hydrophilic small molecule ARV drugs, and may expand the nanocarrier systems being investigated for HIV prevention or treatment.
Topical, mucosal intervention of HIV is a leading strategy in the efforts to curb the spread of viral infection. A significant research thrust in the field has been to characterize different dosage forms for formulation of physicochemically diverse antiretroviral drugs. Nanocarriers have been used to formulate and deliver small molecule and protein drugs for a range of applications, including ARV drugs for HIV treatment. The broad significance of our work includes evaluation of lipid-shell, hydrogel-core nanoparticles for formulation and topical, vaginal delivery of two water-soluble antiretroviral drugs. We have characterized these nanocarriers for their physical properties and their biological activity against HIV-1 infection in vitro, and demonstrated the ability to deliver drug-loaded nanocarriers in vivo.
纳米载体是用于药物递送的多功能载体，并正在成为在单一系统中配制和递送多种抗逆转录病毒（ARV）药物的平台。在此，我们描述了水凝胶核心和脂质壳纳米颗粒（纳米脂质凝胶）的制备，用于控制马拉维若（MVC）和替诺福韦酯富马酸盐（TDF）的负载以及局部阴道递送，这两种ARV药物具有不同的作用机制，用于治疗HIV。纳米脂质凝胶平台被成功用于配制MVC和TDF，制备出负载ARV药物的纳米脂质凝胶，并对其物理性质和在细胞培养中对HIV-1 BaL的抗病毒活性进行了表征。我们还表明，在小鼠模型中将这些药物载体局部施用于阴道黏膜会导致宫颈阴道灌洗液中对HIV-1 BaL产生抗病毒活性。我们的结果表明，纳米脂质凝胶载体有望用于亲水性小分子ARV药物的包封和递送，并可能扩展正在研究用于HIV预防或治疗的纳米载体系统。
HIV的局部黏膜干预是遏制病毒感染传播努力中的一项主要策略。该领域的一项重要研究重点是表征用于配制物理化学性质多样的抗逆转录病毒药物的不同剂型。纳米载体已被用于配制和递送小分子和蛋白质药物，用于一系列应用，包括用于HIV治疗的ARV药物。我们工作的广泛意义包括评估脂质壳、水凝胶核心纳米颗粒用于配制和局部阴道递送两种水溶性抗逆转录病毒药物。我们已经对这些纳米载体的物理性质及其在体外对HIV-1感染的生物活性进行了表征，并证明了在体内递送负载药物的纳米载体的能力。
