Wu Xiao, Griffin Peter, Price Gareth J, Guy Richard H
Department of Pharmacy, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Mol Pharm. 2009 Sep-Oct;6(5):1449-56. doi: 10.1021/mp900119u.
The skin disposition of topically applied nanoparticles with varying degrees of hydrophobicity, composed of different proportions of polystyrene (PS) and poly-(2-hydroxyethyl methacrylate) (HEMA), and of an associated, model "active" (Nile Red), was investigated. PS-HEMA copolymer nanoparticles were fluorescently labeled, via the covalent incorporation of a small quantity of fluorescein methacrylate, and characterized by dynamic light scattering, transmission electron microscopy and NMR. The fluorophore, Nile Red, was dispersed into the nanoparticles and its loading was determined by ultracentrifugation. Skin uptake was assessed in vitro following a 6 h application of the nanoparticle formulation, via stratum corneum (SC) tape-stripping and confocal microscopy. Nanoparticle diameters were below 100 nm. Progressive introduction of HEMA decreased particle hydrophobicity and reduced Nile Red loading. Uptake of Nile Red into the skin, as assessed both by the amounts extracted from the SC and by confocal microscopy, decreased as the percentage HEMA increased. Confocal microscopy confirmed that nanoparticles could not move beyond the superficial SC, but did show affinity for hair follicle openings. In conclusion, the loading of a lipophilic "active" into nanoparticles, and its subsequent release when these formulations are applied topically, are sensitive to the composition and relative hydrophobicity of the carrier.
研究了由不同比例的聚苯乙烯（PS）和聚甲基丙烯酸2-羟乙酯（HEMA）组成的、具有不同程度疏水性的局部应用纳米颗粒以及一种相关的模型“活性成分”（尼罗红）的皮肤分布情况。通过少量甲基丙烯酸荧光素的共价掺入对PS-HEMA共聚物纳米颗粒进行荧光标记，并通过动态光散射、透射电子显微镜和核磁共振进行表征。将荧光团尼罗红分散到纳米颗粒中，并通过超速离心法测定其负载量。在纳米颗粒制剂应用6小时后，通过角质层（SC）胶带剥离和共聚焦显微镜在体外评估皮肤摄取情况。纳米颗粒直径低于100nm。逐步引入HEMA会降低颗粒疏水性并减少尼罗红负载量。通过从SC中提取的量和共聚焦显微镜评估，随着HEMA百分比的增加，尼罗红进入皮肤的摄取量减少。共聚焦显微镜证实纳米颗粒无法移动到浅表SC之外，但确实显示出对毛囊开口有亲和力。总之，将亲脂性“活性成分”负载到纳米颗粒中，以及这些制剂局部应用时其随后的释放，对载体的组成和相对疏水性敏感。
