Department of Chemistry, The University of Alabama at Birmingham, 901 14thSt South, CHEM294, Birmingham, AL, 35294, USA.
Department of Biomedical Engineering, The University of Alabama at Birmingham, 1075 13th Street South, Birmingham, AL 35294, USA.
J Colloid Interface Sci. 2017 Nov 15;506:589-602. doi: 10.1016/j.jcis.2017.07.084. Epub 2017 Jul 22.
We report nanothin temperature-responsive hydrogel films of poly(N-vinylcaprolactam) nanoparticles (νPVCL) with remarkably high loading capacity for topical drug delivery. Highly swollen (νPVCL) multilayer hydrogels, where n denotes the number of nanoparticle layers, are produced by layer-by-layer hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with linear PVPON followed by cross-linking of the acrylic acid shell with either ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a (νPVCL) film undergoes dramatic and reversible swelling up to 9 times its dry thickness at pH = 7.5, indicating 89v/v % of water inside the network. These hydrogels exhibit highly reversible ∼3-fold thickness changes with temperature variations from 25 to 50°C at pH = 5, the average pH of human skin. We also show that a (νPVCL) hydrogel loaded with ∼120µgcm sodium diclofenac, a non-steroidal anti-inflammatory drug used for osteoarthritis pain management, provides sustained permeation of this drug through an artificial skin membrane for up to 24h at 32°C (the average human skin surface temperature). The cumulative amount of diclofenac transported at 32°C from the (νPVCL) hydrogel after 24h is 12 times higher than that from the (νPVCL) hydrogel at 22°C. Finally, we demonstrate that the (νPVCL) hydrogels can be used for multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within the νPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we observed the presence of separate dye-loaded νPVCL compartments within the hydrogel matrix with all three dyes confined to the nanogel particles without intermixing between the dyes. Our study provides opportunity for development of temperature-responsive multilayer hydrogel coatings made via the assembly of core-shell nanogel particles which can be used for skin-sensitive materials for topical drug delivery.
我们报告了一种聚（N-乙烯基己内酰胺）纳米粒子（νPVCL）的纳米薄温敏水凝胶薄膜，其具有用于局部药物输送的高载药能力。高度溶胀的（νPVCL）多层水凝胶，其中 n 表示纳米粒子层的数量，是通过核壳 PVCL-co-丙烯酸纳米粒子与线性 PVPON 层层氢键组装，然后用乙二胺（EDA）或己二酰肼（AAD）交联丙烯酸壳来制备的。我们证明，（νPVCL）薄膜在 pH=7.5 时会发生剧烈且可重复的溶胀，最大可达其干厚度的 9 倍，表明网络内有 89v/v%的水。这些水凝胶在 pH=5（人体皮肤的平均 pH 值）时，在 25 至 50°C 之间的温度变化下表现出高度可逆的约 3 倍厚度变化。我们还表明，负载约 120µgcm 二氯芬酸钠（一种用于骨关节炎疼痛管理的非甾体抗炎药）的（νPVCL）水凝胶在 32°C（人体皮肤表面平均温度）下通过人工皮肤膜持续渗透这种药物长达 24 小时。在 32°C 下，从（νPVCL）水凝胶中输送的二氯芬酸钠的累积量是在 22°C 下的 12 倍。最后，我们证明通过在核壳纳米凝胶粒子中包含尼罗红、荧光素和 DAPI 染料，在组装水凝胶之前，可以将（νPVCL）水凝胶用于多种药物输送。通过共焦显微镜观察到在水凝胶基质中存在单独的染料负载的 νPVCL 隔室，所有三种染料都被限制在纳米凝胶颗粒内，而染料之间没有混合。我们的研究为通过组装核壳纳米凝胶粒子开发温度响应多层水凝胶涂层提供了机会，这些涂层可用于皮肤敏感材料的局部药物输送。
