Palliyage Gayathri Heenatigala, Hussein Noor, Mimlitz Michael, Weeder Catherine, Alnasser Marya Hassan A, Singh Somnath, Ekpenyong Andrew, Tiwari Amit K, Chauhan Harsh
Creighton University, Omaha, Nebraska, 68178, USA.
Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, Frederic and Mary Wolfe Center, 3000 Arlington Ave., MS 1015, Toledo, Ohio, 43614, USA.
Pharm Res. 2021 May;38(5):851-871. doi: 10.1007/s11095-021-03043-7. Epub 2021 May 12.
Polyphenols such as curcumin (Cur) and resveratrol (Res) have been recently shown to have potential to inhibit proliferation of highly aggressive melanoma cells. This study was designed to investigate the feasibility of a topical delivery system, using a solid lipid nanoparticles (SLNs) loaded delivery systems, that can enhance the skin penetration and anti-cancer efficacy of combination of these polyphenols. Negatively charged Cur-Res SLNs with a mean diameter of 180.2 ± 7.7 nm were prepared using high shear homogenization method. Cur-Res SLNs were found to be stable up to 2 weeks under 4°C. The in vitro release study showed that Res was released five time more than curcumin. The permeability of resveratrol was about 1.67 times that of curcumin from the SLN-gel formulation which was significantly (p < 0.05) lower than from SLN suspension. More than 70% of Cur-Res SLNs were bound to skin locally in a skin binding study suggesting potentially utility of Cur-Res SLNs in the treatment of localized melanoma. In fact, the electrical cell-substrate impedance sensing (ECIS) measurements suggested that Cur-Res combination has potential to stop cell migration of B16F10 melanoma cells. Furthermore, both, Cur-Res SLNs and Cur-Res solution at the ratio of 3:1 demonstrated a strong synergistic inhibition of SK-MEL-28 melanoma cell proliferation. Further evaluation of Cur-Res SLNs in vivo melanoma models are warranted to establish the clinical utility of Cur-Res formulations in melanoma therapy.
姜黄素（Cur）和白藜芦醇（Res）等多酚类物质最近被证明有抑制高侵袭性黑色素瘤细胞增殖的潜力。本研究旨在探讨一种局部给药系统的可行性，该系统使用负载固体脂质纳米粒（SLNs）的给药系统，可增强这些多酚类物质组合的皮肤渗透和抗癌效果。采用高剪切均质法制备了平均直径为180.2±7.7nm的带负电荷的Cur-Res SLNs。发现Cur-Res SLNs在4℃下可稳定保存2周。体外释放研究表明，Res的释放量是姜黄素的五倍。白藜芦醇从SLN-凝胶制剂中的渗透率约为姜黄素的1.67倍，显著低于（p<0.05）从SLN悬浮液中的渗透率。在一项皮肤结合研究中，超过70%的Cur-Res SLNs在局部与皮肤结合，表明Cur-Res SLNs在治疗局部黑色素瘤方面可能具有实用性。事实上，细胞-基质阻抗传感（ECIS）测量表明，Cur-Res组合有潜力阻止B16F10黑色素瘤细胞的迁移。此外，Cur-Res SLNs和比例为3:1的Cur-Res溶液均对SK-MEL-28黑色素瘤细胞增殖表现出强烈的协同抑制作用。有必要在体内黑色素瘤模型中进一步评估Cur-Res SLNs，以确定Cur-Res制剂在黑色素瘤治疗中的临床实用性。
