Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma

Abstract

Fisetin (Fis), a natural flavonoid with anticancer effects, suffers from delivery constraints. Fisetin-nanostructured lipid carriers (NLCs) were developed for better efficacy against metastatic melanoma, employing the design of experiment (DoE) approach. The optimized NLCs depict a particle diameter of 135.0 ± 5.5 nm, a polydispersity index (PDI) of 0.176 ± 0.035, and an entrapment efficiency of 78.16 ± 1.58%. The formulation was stable over a period of 60 days and demonstrated sustained release of the drug (74.79 ± 3.75%) over 96 h. Fis-NLCs depicted at least ∼3.2 times lower IC 50 value and ∼1.8 times higher drug uptake at 48 h in A-375 and B16F10 cells compared to that of Fis. It also inhibited the mobility of melanoma cells and induced cell cycle arrest at the G1/S phase. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot results show enhanced expression of Nrf2/NQO1 genes and an apoptotic effect by the upregulation of BAX mRNA expression. The protein levels of BAX and p53 were ∼2-fold higher compared with that of pure Fis. In-vivo studies demonstrated 5.9-and 10.7-fold higher inhibition in melanoma-associated metastasis in the lungs and liver, respectively. The outcomes from this study demonstrated Fis-NLCs as an effective tool against melanoma.

The development of nanocarriers for natural products

“…Moreover, because of its core structure of 4-keto and 7-OH groups, FST demonstrates powerful antiinflammatory and antitumor effects in cellular and animal models of human diseases (Ren et al, 2020;Syed et al, 2016;. However, its clinical development is hindered by low water solubility (10.45 μg/mL) and poor oral bioavailability (44.1%) (Kumar et al, 2023). These limitations of FST can be potentially mitigated using nanocarriers.…”

“…The NPs demonstrated stability over a period of 60 days and sustains drug release for 96 h, which enhanced the sustained-release capability of FST. In melanoma cells and mouse models, these FST-NLCs notably increased apoptosis and antioxidant activity while concurrently inhibiting melanoma metastasis to the lungs and liver, effectively improving the anticancer potency and targeting of FST (Kumar et al, 2023).…”