Release kinetics and cancer cell cytotoxicity of quercetin from polymer coated deformable lipid-based nanocarriers

Abstract

The development of safer treatment alternatives for cancer and other chronic illnesses still calls for innovation. Chemopreventive agents (e.g., quercetin, QR) are often sought after for therapeutic and palliative care. However, poor aqueous solubility, chemical instability, and low bioavailability limit their use. With this in mind, we evaluated the potential for synergistic effects among cholesterol, surfactants, and non-covalent polymer coatings (polyethylene glycol and chitosan) in transferosomes. Dispersions of L-α-phosphatidylcholine and cholesterol were prepared by the thin-film hydration method and ultrasonication. Non-ionic, anionic, and cationic surfactants: poloxamer-407, sodium deoxycholate (SDC), and cetyltrimethylammonium bromide (CTAB), respectively, were added to regulate the deformability of the cholesterol-containing lipid bilayers.

CTAB-QR-transferosomes released the highest amount of QR, 86.50 ± 0.54%, in 24 h, with a particle size of 284.54 ± 28.4 nm, zeta potential of 20.2 ± 10.6 mV, viscosity of 11.19 ± 4.96 cP, entrapment efficiency of 99.1 ± 0.1%, and drug loading capacity of 13.56 ± 0.01%. The QR-loaded lipid-based nanocarriers with the cholesterol/CTAB intra-membrane modulators were then separately coated with polyethylene glycol (PEG) and chitosan to test for a potential synergistic effect of the polymers on membrane interactions with HepG2, A594, and U937 cell lines. The polymer-coated cholesterol/surfactant-regulated lipid vesicles did not make a statistically significant contribution to cytotoxicity against HepG2 cells compared with free quercetin.

However, the synergy between CTAB and PEG resulted in a greater increase in cytotoxicity against A594 cells than the CTAB/Chitosan combination. None of the polymeric coatings provided an additional increase in efficacy against U937 cells compared with uncoated transferosomes containing cholesterol and CTAB. To our knowledge, this is the first exploration of possible synergistic contributions between antagonistic intra-membrane modulators and polymer coatings on transferosomes to evaluate potential benefits of enhanced cytotoxicity against cancerous cells in vitro.

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Agiba, A.M., Lorenzo-Anota, H.Y., Galván-Marroquín, J.E. et al. Release kinetics and cancer cell cytotoxicity of quercetin from polymer coated deformable lipid-based nanocarriers. J Nanopart Res 28, 11 (2026). https://doi.org/10.1007/s11051-025-06529-2

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