Synergistically active curcumin resveratrol solid lipid nanoparticles for treatment of melanoma
Poorly soluble polyphenols such as curcumin and resveratrol have shown significant potential in the treatment of melanoma due to their multifarious roles in its pathogenesis. Furthermore, the combination of curcumin and resveratrol was found to demonstrate synergistic effects in other cancers; colorectal, breast cancer. However, the highly hydrophobic properties and the excellent barrier function of the skin lead to a very low percutaneous penetration of curcumin and resveratrol. In this context, topical solid lipid nanoparticles were introduced as a drug carrier to enhance the skin penetration of the aforementioned polyphenols and exploit their anti-cancer activity. Small, negatively charged curcumin and resveratrol loaded SLNs (Cur-Res SLNs) with a mean diameter of 180.17 ± 7.69 nm were prepared using high shear homogenization method. Cur-Res SLNs were found to be more stable up to 3 2 weeks under 4°C. In vitro release study showed that showed that release profile of curcumin was significantly low compared to resveratrol. Binding studies demonstrated that a significant amount of Cur-Res SLNs got bound to the skin, indicating that these SLNs are ideal systems for topical administration of curcumin, resveratrol and their combinations. ECIS measurements indicate that combination of curcumin and resveratrol has potential to stop cell migration of B16F10 melanoma cells. Both Cur-Res SLNs and solution of curcumin and resveratrol at the ratio of 3:1 demonstrated a strong synergism on the cytotoxicity of SK-MEL-28 cell line. However, one of the limitations of this study is low drug loading which is not adequate for the in vivo performances. Therefore, in future studies, formulation parameters of Cur-Res SLNs should be further optimized to increase the drug loading.
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