目的:5-氟尿嘧啶(5-FU)生物利用度很低,不能口服,不良反应严重。因此,这项研究的主要目的是开发,评估,并比较不同纳米制剂局部应用对不同类型皮肤皮肤癌的化学预防效果。
方法:蓖麻油(油),TranscutolHP(表面活性剂),和聚乙二醇(PEG)-400(助表面活性剂)已经在非离子性质和最高纳米乳液(NE)区域的基础上。采用水微滴定法与超声处理法(基于高能)制备5-FU-NE。优化的-5-FU-NE是热力学稳定的,它们的特征是根据小球的大小进行的,zeta电位,折射率,和粘度。优化的NE已在Carbopol®934的帮助下转化为5-FU-NE-Gel,并在不同的皮肤中进行了渗透研究(牛,山羊,和老鼠,离体)使用Logan透皮扩散细胞(DHC-6T)。优化的-5-FU-NE和5-FU-NE-凝胶对黑色素瘤细胞系进行了细胞毒性研究(体外)。
结果:用于大鼠皮肤模型的5-FU-NE-Gel纳米制剂的5-FU的渗透比5-FU-NE高1.56倍,并且比5-FU-S高12.51倍。大鼠皮肤的5-FU-NE-凝胶的稳态通量和渗透系数的值较高,分别为12.0244±1.12µgcm-2h-1和1.2024±0.073×10-2µgcm-2h-1。发现优化的-5-FU-NE和5-FU-NE-凝胶纳米制剂是物理稳定的。SK-MEL-5癌细胞已经显示基于细胞毒性研究(体外)的结果,作为优化的-5-FU-NE-凝胶的5-FU比5-FU-NE随后是游离的5-FU有效得多。5-FU-NE-凝胶中5-FU的定位更高,在大鼠皮肤中的渗透性更高。
结论:发现5-FU-NE-凝胶可更好地治疗皮肤恶性肿瘤。它可以开发5-FU-NE-凝胶可能是皮肤癌化学预防的有前途的载体。
OBJECTIVE: 5-Fluorouracil (5-FU) can\'t be given orally because of very low bioavailability and produces serious adverse effects. Therefore, the main objective of this research is to develop, evaluate, and comparative effects by different nanoformulations of topical application on chemoprevention of skin cancer in different types of skin.
METHODS: Castor oil (oil), Transcutol HP (surfactant), and Polyethylene glycol (PEG)-400 (co-surfactant) have taken on the basis of nonionic property and highest nanoemulsion (NE)-region. Aqueous micro titration method with ultra-sonication method (based on high energy) was used for the preparation of 5-FU-NE. Optimized-5-FU-NE was stable thermodynamically, and their characterizations was performed on the basis of globule size, zeta potential, refractive index, and viscosity. Optimized-NE has been converted into 5-FU-NE-Gel with the help of Carbopol® 934 and also performed their permeation studies in the different skins (cow, goat, and rat, ex vivo) using Logan transdermal diffusion cell (DHC-6T). Optimized-5-FU-NE and 5-FU-NE-Gel were evaluated cytotoxic studies (in vitro) on the melanoma cell lines.
RESULTS: The permeation of 5-FU from 5-FU-NE-Gel nanoformulation for rat skin model was 1.56 times higher than the 5-FU-NE and 12.51 times higher than the 5-FU-S for the cow and goat skin model. The values of steady state flux and permeability coefficient for 5-FU-NE-Gel of rat skin were higher i.e. 12.0244 ± 1.12 µgcm-2h-1 and 1.2024 ± 0.073 × 10-2 µg cm-2h-1, respectively. Optimized-5-FU-NE and 5-FU-NE-Gel nanoformulation were found to be physically stable. SK-MEL-5 cancer cells have showed the results based on cytotoxicity studies (in vitro) that 5-FU as Optimized-5-FU-NE-Gel is much more efficacious than 5-FU-NE followed by free 5-FU. Localization of 5-FU from 5-FU-NE-Gel was higher with higher permeation in rat skin.
CONCLUSIONS: 5-FU-NE-Gel is found to be for the better to treatment of cutaneous malignancies. It can be developed 5-FU-NE-Gel could be a promising vehicle for the skin cancer chemoprevention.