College of Pharmacy-Glendale, Department of Pharmaceutical Sciences, Midwestern University, Glendale Hall 236-14, 19555 N. 59th Avenue, Glendale, AZ 85308, USA.
J Biomed Nanotechnol. 2012 Dec;8(6):944-56. doi: 10.1166/jbn.2012.1460.
In recent years, diverse nanoemulsion vehicles (NEs) have been developed with vast potential for improving therapeutic index of clinically approved and experimental drugs. Using oils rich in omega-3 and omega-6 polyunsaturated fatty acids (PUFA), several promising nanoemulsion formulations have been developed recently for oral and systemic administration. The aim of our present work is to successfully develop and characterize optimized nanoemulsion platform, using the PUFA-rich argan oil that contain several important anti-inflammatory and antimitotic natural components. Using various emulsifying mixtures of polyethoxylated solutol HS-15 and polyethyleneglucol Vitamin E succinyl ester (TPGS), to form different NEs showing extended shelf-life stability. The physicochemical properties of prototype argan NEs were analyzed and utilizing a 32 full factorial design, followed by biocompatibility screen, using normal vascular myocytes and areolar fibroblasts. While 90-180 day stability of NEs correlated with TPGS:solutol surfactant blend ratios, adverse effects on integrity of test cultures were only noted at high TPGS content in the emulsifier system, exceeding 80%. Finally, the anti-proliferative efficacy of selected stable and acceptably biocompatible nanoscale TPGS-emulsified argan oil formulations was investigated using murine breast and colon carcinoma cells. The IC50 values of the combination of argan oil and TPGS (40-80% wt of emulsifiers) were 5-9 folds lower compared to TPGS-free and argan-oil free control NEs. Argan oil NE, stabilized with Vitamin E TPGS and solutol HS mixtures, demonstrated significant pro-apoptotic effect on both test cancer cell lines, indicating built-in anticancer properties for such NE platform, potentially enhancing overall antineoplastic effects of incorporated candidate chemotherapeutic agents.
近年来，开发了多种纳米乳剂载体（NE），具有极大的潜力来提高临床批准和实验药物的治疗指数。最近，使用富含ω-3 和 ω-6 多不饱和脂肪酸（PUFA）的油，已经开发了几种有前途的纳米乳剂制剂，用于口服和全身给药。我们目前的工作旨在成功开发和表征优化的纳米乳剂平台，使用富含 PUFA 的摩洛哥坚果油，其中含有几种重要的抗炎和抗有丝分裂天然成分。使用聚氧乙烯化 Solutol HS-15 和聚乙二醇维生素 E 琥珀酸酯（TPGS）的各种乳化混合物，形成不同的 NE，显示出延长的货架期稳定性。原型摩洛哥坚果 NE 的物理化学性质进行了分析，并利用 32 个完全因子设计，随后进行了生物相容性筛选，使用正常血管平滑肌细胞和疏松成纤维细胞。而 NE 的 90-180 天稳定性与 TPGS：Solutol 表面活性剂混合物的比例相关，只有在乳化剂系统中的 TPGS 含量高（超过 80%）时，才会对测试培养物的完整性产生不利影响。最后，使用小鼠乳腺癌和结肠癌细胞研究了选定的稳定且可接受的生物相容的纳米级 TPGS 乳化摩洛哥坚果油制剂的抗增殖功效。与不含 TPGS 和不含摩洛哥坚果油的对照 NE 相比，含油和 TPGS（乳化剂 40-80%wt）的组合的 IC50 值低 5-9 倍。用维生素 E TPGS 和 Solutol HS 混合物稳定的摩洛哥坚果油 NE，对两种测试癌细胞系均表现出显著的促凋亡作用，表明这种 NE 平台具有内在的抗癌特性，可能增强了所包含候选化疗药物的整体抗肿瘤作用。
