Combination of hydrotropic nicotinamide with nanoparticles for enhancing tacrolimus percutaneous delivery.
Combination of hydrotropic nicotinamide with nanoparticles for enhancing tacrolimus percutaneous delivery.
复制标题
水溶助长烟酰胺与纳米颗粒的组合用于增强他克莫司经皮递送
DOI：
10.2147/ijn.s108545
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发表时间：
2016
影响因子：
8
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Pan W;Qin M;Zhang G;Long Y;Ruan W;Pan J;Wu Z;Wan T;Wu C;Xu Y
他克莫司（FK 506）是一种有效的免疫抑制剂，用于治疗炎症性皮肤病，由于其高疏水性和分子量，几乎不渗透进入和通过皮肤。本研究的目的是开发一种基于烟酰胺（NIC）和包封FK 506的纳米颗粒（NPs）的混合系统，如FK 506-NPs-NIC，以促进经皮给药，该系统利用NIC和NPs的优点来获得协同效应。进行溶解度和经皮渗透研究。结果表明，NIC能提高FK 506的溶解度和渗透性，且20%（w/v）NIC对FK 506的渗透性更好，因此选择NIC作为增溶FK 506的水溶性溶液，制备FK 506-NPs-NIC。将透明质酸（HA）与胆固醇（Chol）化学偶联得到HA-Chol的两亲性偶联物，其在含有FK 506的20%NIC溶液中自组装纳米粒。纳米粒子的粒径，zeta电位，和形态进行了表征。在NIC存在和不存在的情况下，评价纳米粒的包封率和体外经皮渗透。结果表明，水溶增溶的FK 506易于包封到具有较高包封率（79.2%± 4.2%）的NPs中，并且NPs与NIC的组合对FK 506在皮肤内的沉积（2.39±0.53 μg/cm 2）和通过皮肤的渗透（13.38±2.26 μg/cm 2）表现出显著的协同作用。通过体内渗透研究，通过共聚焦激光扫描显微镜进一步观察NPs与NIC的组合对药物渗透的影响，并且结果证实NPs-NIC协同增强药物向皮肤中的渗透。在HaCaT细胞中进行的细胞摄取呈现NPs对细胞摄取的促进作用。这些结果表明，HA-Chol-NPs-NIC可以协同改善FK 506的经皮给药，这是一种基于FK 506纳米载体治疗皮肤疾病的新的潜在策略。
Tacrolimus (FK506), an effective immunosuppressant for treating inflammatory skin diseases, hardly penetrates into and through the skin owing to its high hydrophobicity and molecular weight. The aim of this study was to develop a hybrid system based on nicotinamide (NIC) and nanoparticles (NPs) encapsulating FK506, such as FK506–NPs–NIC, for facilitating percutaneous delivery, which exploited virtues of both NIC and NPs to obtain the synergetic effect. Solubility and percutaneous permeation studies were carried out. The results showed that NIC could increase the solubility and permeability of FK506 and that 20% (w/v) NIC presented higher FK506 permeability and was thus chosen as the hydrotropic solution to solubilize FK506 and prepare FK506–NPs–NIC. Hyaluronic acid (HA) was chemically conjugated with cholesterol (Chol) to obtain amphiphilic conjugate of HA–Chol, which self-assembled NPs in 20% NIC solution containing FK506. The particle size, zeta potential, and morphology of NPs were characterized. The encapsulation efficiency and in vitro percutaneous permeation of NPs were evaluated in the presence and absence of NIC. The results demonstrated that hydrotropic solubilizing FK506 was readily encapsulated into NPs with a higher encapsulation efficiency of 79.2%±4.2%, and the combination of NPs with NIC exhibited a significantly synergistic effect on FK506 deposition within the skin (2.39±0.53 μg/cm2) and penetration through the skin (13.38±2.26 μg/cm2). The effect of the combination of NPs with NIC on drug permeation was further visualized by confocal laser scanning microscope through in vivo permeation studies, and the results confirmed that NPs–NIC synergistically enhanced the permeation of the drug into the skin. The cellular uptake performed in HaCaT cells presented a promoting effect of NPs on cellular uptake. These overall results demonstrated that HA–Chol–NPs–NIC can synergistically improve the percutaneous delivery of FK506, and it is a novel potential strategy based on a nano-sized carrier for FK506 to treat skin diseases.