Abstract 824: Statistical optimization of stable Quercetin nanoparticles for tumor targeting

Abstract

Quercetin is a well-known flavonoid with a significant in vitro anticancer effect and low toxicity profile. Despite of that, its clinical use is still limited because of its low solubility, bioavailability, and instability in physiological conditions. The aim of this study was to develop and optimize stable quercetin nanoparticles targeting tumor cells within the body. Quercetin nanoparticles were synthesized using solvent emulsification technique using zein, beta-cyclodextrin, and pectin at different concentrations. The prepared formulations were optimized using factorial response surface analysis. The stability of the optimized quercetin nanoparticles in conditioned media, obtained from subculture of colorectal cancer cell line HCT-116, was compared to the stability of the free drug powder over 24 h. Moreover, the cytotoxic effect of Quercetin powder and the optimized Quercetin nanoparticles were evaluated against two colorectal cancer lines (HT-29, and HCT116), using MTT assay, under normoxic conditions. Annexin-V/FITC apoptotic assay was used to detect the number of cells that underwent apoptosis using flow cytometry. The optimized formulation was composed of 10 mg of zein and 31.35 mg beta-cyclodextrin, with no pectin. It had particle size of 221 nm, polydispersity index of 0.115, zetapotential of 7.65 mV. The stability of the optimized quercetin nanoparticles in the conditioned media of HCT-116 was significantly higher than the free drug powder over 24 h. In HT-29, the optimized nanoparticles and the free drug had IC50 of 29.33 µM and 60.78 µM, respectively. In HCT-116, optimized nanoparticle and the free drug had IC50’s 31.11 µM and 59.20 µM, respectively. The flow cytometric analysis after annexin-V/FITC staining showed that treatment with the optimized quercetin nanoparticles significantly induced total apoptosis in the two colorectal cancer lines (HT-29 and HCT 116) when compared to the free drug and plain nanoparticles. In conclusion, the optimized quercetin nanoparticles were found to be capable of increasing drug stability in physiological fluids as well as increasing its cytotoxic effect in two colorectal cancer cell lines by apoptosis induction when compared to the drug in powder form as well as plain nanoparticles. Citation Format: Nourhan Khaled Hassan, Eman El-labbad, Jayalakshmi jagal, Mohamed Haider, Ibrahim El-sayed. Statistical optimization of stable Quercetin nanoparticles for tumor targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 824.