Department of Biomedical Engineering, Yale University, USA.
J Control Release. 2011 Dec 10;156(2):258-64. doi: 10.1016/j.jconrel.2011.06.036. Epub 2011 Jul 8.
Intravaginal (ivag) delivery, which is a proven way to confer local protection against STDs contracted via the reproductive tract, is complicated by the mucus gel barrier, the hormone cycle, and the harsh mucosal environment that leads to low residence-time for administered agents. Polymer delivery vehicles may be useful in overcoming these barriers. In this study, we explored the fate of nanoparticles (NP) made from poly(lactide-co-glycolide) (PLGA) in the mouse reproductive tract after ivag delivery. The nanoparticles were modified to display avidin (Avid-NP) or 2 kDa PEG (PEG-NP) on their surface. Vaginal retention fractions for both muco-adhesive Avid-NP and stealthy PEG-NP were 5× higher than unmodified PLGA particles (NP). The amount of particles associated with mucus differed across formulations (Avid-NP>NP>PEG-NP). PEG-NP was found at higher concentration in the tissue than Avid-NP and NP up to 6h after delivery, and particles were found within epithelial cells, the underlying submucosal stromal and fibroblast cells of the vaginal tissue. Our results demonstrate that surface properties of nanoparticles can impact their fates following ivag delivery. Moreover, we show that the muco-evasive PEG-modified nanoparticles are the most effective among the delivery vehicles tested for this application.
阴道内（ivag）给药是一种已被证实的方法，可以提供针对通过生殖道感染的性传播疾病的局部保护，但受到粘液凝胶屏障、激素周期和恶劣的粘膜环境的影响，导致给予的药物在体内停留时间较短。聚合物给药载体可能有助于克服这些障碍。在这项研究中，我们探讨了经阴道内给药后，由聚（乳酸-共-乙醇酸）（PLGA）制成的纳米颗粒（NP）在小鼠生殖道中的命运。将纳米颗粒修饰为在其表面显示亲和素（Avid-NP）或 2 kDa PEG（PEG-NP）。与未修饰的 PLGA 颗粒相比，具有粘膜粘附性的 Avid-NP 和隐形 PEG-NP 的阴道保留分数高 5 倍。不同配方的颗粒与粘液的结合量不同（Avid-NP>NP>PEG-NP）。在给药后 6 小时内，PEG-NP 在组织中的浓度高于 Avid-NP 和 NP，并且在阴道组织的上皮细胞、下层粘膜下基质和成纤维细胞中发现了颗粒。我们的结果表明，纳米颗粒的表面特性会影响其在阴道内给药后的命运。此外，我们表明，在测试的这种应用的给药载体中，具有粘膜逃避性的 PEG 修饰的纳米颗粒是最有效的。
