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Tarek A Ahmed,1,2 Ghada A Milibary,1 Alshaimaa M Almehmady,1 Amerh A Alahmadi,1 Ehab MM Ali,3 Khalid M El-Say1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Centre for Artificial Intelligence in Precision Medicine, King Abdulaziz University, Alsulaymanyah, Jeddah, 21589, Saudi Arabia; 3Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Tarek A Ahmed, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia, Tel +96626400000 ext 22250, Email tabdelnapy@kau.edu.saBackground: This study investigates the influence of various formulation parameters on the characteristics of hinokitiol-loaded phytosomes and evaluates their anticancer potential against breast cancer cells.Materials and Methods: Phytosomal nanoparticles were prepared and characterized for size, zeta potential, and entrapment efficiency. Morphological analysis was conducted using optical microscopy and transmission electron microscopy (TEM). The solubility of hinokitiol at different pH levels was determined, and the in vitro release profile of the optimized phytosomes was assessed. Cytotoxicity assays were performed to evaluate the anticancer efficacy against breast cancer cell lines, and apoptosis induction was examined using Annexin V/propidium iodide staining. Cell cycle analysis was conducted to assess the impact on cell cycle progression.Results: The optimized phytosomes demonstrated a size range of 138.4 ± 7.7 to 763.7 ± 15.4 nm, with zeta potentials ranging from − 10.2 ± 0.28 to − 53.2 ± 1.06 mV and entrapment efficiencies between 29.161 ± 1.163% and 92.77 ± 7.01%. Morphological characterization confirmed uniformity and spherical morphology. Hinokitiol solubility increased with pH, and the release from the optimized phytosomes exhibited sustained patterns. The formulated phytosomes showed superior cytotoxicity, with lower IC50 values compared to pure hinokitiol. Treatment induced significant apoptosis and cell cycle arrest at the G2/M and S phases.Conclusion: Hinokitiol-loaded phytosomes demonstrate promising anticancer efficacy against breast cancer cells, highlighting their potential as targeted therapeutic agents for breast cancer therapy.Keywords: hinokitiol, phytosomes, cytotoxic activity, breast cancer, apoptosis, cell cycle

Background: Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations., Materials and Methods: Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed., Results: The prepared formulations were in the nano-size range (34.01 ± 2.00-278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC 50 against MCF-7 (4.51 µg/mL) and T47D (8.22 µg/mL) cancer cells. When T47D cells were treated with IC 50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC 50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death., Conclusion: These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Ahmed et al.)