Background: Luteolin is a flavonoid compound that has been widely studied for its various anti-cancer properties and sensitization to multidrug-resistant cells. However, the limited solubility and bioavailability of Lut hindered its potential clinical use. Theoretically, the combination of this compound with vitamin E TPGS and poloxamer 407 can produce a synergistic effect to enhance tumor apoptosis and P-glycoprotein inhibition. This study aimed to develop and optimize vitamin E TPGS/Poloxamer 407 micelles loaded with luteolin through investigating certain factors that can affect the encapsulation efficiency and particle size of the micelle. Methods: A micelle was prepared using the film hydration method, and the micellar solution was lyophilized. The cake formed was analyzed. The factors investigated include the concentrations of the surfactants, ratio of vitamin E TPGS/Poloxamer 407, temperature of the hydrating solution, duration of hydration, and freezing temperature before lyophilization. The effects of these factors on the encapsulation efficiency and particle size of the micelle were also studied. The encapsulation efficiency was measured using a UV-Vis spectrophotometer, while particle size was measured using dynamic light scattering. Results: The optimized micelle was found to have 90% encapsulation efficiency with a particle size of less than 40 nm, which was achieved using a 10% concentration of surfactants at a vitamin E TPGS/Poloxamer 407 ratio of 3:1. The optimized temperature for hydrating the micellar film was 40 °C, the optimized mixing time was 1 h, and the optimized freezing temperature was −80 °C. The solubility of the luteolin-loaded micelles increased 459-fold compared to pure Lut in water. The critical micelle concentration of the vitamin E TPGS/Poloxamer 407 micelle was 0.001 mg/mL, and the release study showed that luteolin-loaded micelles exhibited sustained release behavior. The release of luteolin from a micelle was found to be higher in pH 6.8 compared to pH 7.4, which signified that luteolin could be accumulated more in a tumor microenvironment compared to blood. Conclusion: This study demonstrated that several factors need to be considered when developing such nanoparticles in order to obtain a well-optimized micelle.

With approximately 18 million people affected by cancer in 2020 globally, scientists are exploring innovative approaches to develop effective treatments for various types of cancer. Traditional chemotherapy drugs, although effective against cancer cells, often lead to significant side effects on healthy tissues, such as hair loss, anemia, and nausea. To discover safer alternatives, researchers are investigating natural bioactive compounds found abundantly in plants. Luteolin, a flavonoid found in celery and artichokes, stands out due to its diverse anti-carcinogenic properties, including inhibiting proliferation, inducing apoptosis, activating autophagy, and inhibiting angiogenesis and metastasis. However, the therapeutic potential of luteolin is hindered by challenges related to its bioavailability and solubility. This critical review explores the specific anti-carcinogenic properties of luteolin while analyzing the impact of its limited bioavailability and solubility on effectiveness. Additionally, it investigates the outcomes of encapsulating luteolin in nanoformulations, providing insights into potential strategies for enhancing its anti-carcinogenic effects. Finally, the review compares the efficacy of luteolin with and without nanoformulations. This review provides valuable insights into the potential of utilizing luteolin-loaded nanoformulations as a safer and more effective method for treating cancer, contributing to the ongoing efforts in improving cancer care and outcomes worldwide.