Mei Zhinan, Chen Huabing, Weng Ting, Yang Yajiang, Yang Xiangliang
Pharmaceutical Institute, Huazhong University of Science and Technology, Wuhan, PR China.
Eur J Pharm Biopharm. 2003 Sep;56(2):189-96. doi: 10.1016/s0939-6411(03)00067-5.
Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activities. However, its clinical use is restricted to some content due to its poor water solubility and some toxic effects. In order to find innovative ways for administering TP and alleviating its disadvantages, the controlled release delivery systems such as solid lipid nanoparticle (SLN) and microemulsion have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery capacity and anti-inflammatory activity were also evaluated. The results indicated that these SLN dispersions and microemulsions could serve as efficient promoters for the TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN dispersion consisted of 5% tristearin glyceride, 1.20% soybean lecithin and 3.60% polyethylene glycol (400) monosterate, while the best formulation of microemulsion consisted of 40% isopropyl myristate, 50% Tween-80: 1,2-propylene glycol (5:1, v/v) and water. The steady-state flux (Js) and permeability coefficient (Kp) of triptolide for the SLN dispersion of the first 6 h were 3.1+/-0.4 microg/cm2 per h and 0.0124+/-0.001 cm/h or 6.4+/-0.7 microg/cm2 per h and 0.0256+/-0.002 cm/h for the microemulsion, which was 3.45 and 7.02 times higher than those of triptolide solution, respectively. The anti-inflammatory activity of SLN dispersion was stronger than that of microemulsion in carrageenan induced rat paw edema. However, the results were the reverse in complete Frenud's adjuvant induced paw edema. Further investigations should be carried out on the toxicity of different formulations of triptolide to tissues.
雷公藤甲素（TP）已被证明具有抗炎、免疫抑制、抗生育和抗肿瘤活性。然而，由于其水溶性差和一些毒性作用，其临床应用受到一定限制。为了寻找雷公藤甲素给药的创新方法并减轻其缺点，已开发出如固体脂质纳米粒（SLN）和微乳等控释给药系统。在本文中，我们描述了雷公藤甲素专用给药系统的制备及一些特性表征。还评估了其透皮给药能力和抗炎活性。结果表明，这些SLN分散体和微乳可作为雷公藤甲素渗透皮肤的有效促进剂。此外，本研究对不同配方进行了优化。SLN分散体的最佳配方由5%的三硬脂酸甘油酯、1.20%的大豆卵磷脂和3.60%的聚乙二醇（400）单硬脂酸酯组成，而微乳的最佳配方由40%的肉豆蔻酸异丙酯、50%的吐温80:1,2 - 丙二醇（5:1，v/v）和水组成。雷公藤甲素在SLN分散体中前6小时的稳态通量（Js）和渗透系数（Kp）分别为3.1±0.4μg/cm²·h和0.0124±0.001cm/h，在微乳中为6.4±0.7μg/cm²·h和0.0256±0.002cm/h，分别是雷公藤甲素溶液的3.45倍和7.02倍。在角叉菜胶诱导的大鼠足肿胀模型中，SLN分散体的抗炎活性强于微乳。然而，在完全弗氏佐剂诱导的足肿胀模型中结果相反。应进一步研究雷公藤甲素不同配方对组织的毒性。
