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Novel Curcumin-Resveratrol Solid Nanoparticles Synergistically Inhibit Proliferation of Melanoma Cells

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Abstract

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.

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Authors and Affiliations

  1. Creighton University, Omaha, Nebraska, 68178, USA

    Gayathri Heenatigala Palliyage, Michael Mimlitz, Catherine Weeder, Somnath Singh, Andrew Ekpenyong & Harsh Chauhan

  2. Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, Frederic and Mary Wolfe Center, 3000 Arlington Ave., MS 1015, Toledo, Ohio, 43614, USA

    Noor Hussein, Marya Hassan A Alnasser & Amit K. Tiwari

  3. School of Pharmacy and Health Professionals, Creighton University, Omaha, Nebraska, 68178, USA

    Harsh Chauhan

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  1. Gayathri Heenatigala Palliyage
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Supplementary Information

Supplemental Figure 1

The qualitative analysis of samples by ESI MS in Q1 negative mode (PNG 1007 kb) (PNG 1007 kb)

High Resolution (TIF 12744 kb) (TIF 12744 kb)

Supplemental Figure 2

UV Spectrum of curcumin and resveratrol in Ethanol. Curcumin showed its maximum absorbance at a wavelength of 424 nm, and that for resveratrol was 306 nm (PNG 164 kb) (PNG 164 kb)

High Resolution (TIF 7365 kb) (TIF 7365 kb)

Acknowledgments and Disclosures

The author wishes to acknowledge Creighton University, Omaha, for funding and the use of instruments in completing this project. Dr. Tiwari’s start-up funds (F110760), University of Toledo were used for cell culture studies.

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Palliyage, G.H., Hussein, N., Mimlitz, M. et al. Novel Curcumin-Resveratrol Solid Nanoparticles Synergistically Inhibit Proliferation of Melanoma Cells. Pharm Res 38, 851–871 (2021). https://doi.org/10.1007/s11095-021-03043-7

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