Developing Mixed Micelle Delivery Systems for Aromatase Inhibitors

High Resolution Image Download MS PowerPoint Slide Aromatase, an enzyme that facilitates the last stage in estrogen synthesis (estrogen is identified for a significant impact in the development of breast cancer), has been recognized as a potential target for therapeutic advancements for cancer. Although clinically approved aromatase inhibitors are the cornerstones of estrogen receptor-positive (ER+) breast cancer, their use is often accompanied by adverse side effects and pharmacokinetic limitations, which lead to patient compliance issues and limit therapeutic outcomes. In previous studies, compound 1(a) was identified for its superior inhibition of aromatase with an IC 50 value of 54.0 nM and appreciable tumor growth inhibitory activities. Here, we demonstrated the pharmaceutical capability of 1(a) while evaluating its various features, including acute toxicity, bioavailability by developing a nanodrug delivery system, and therapeutic efficacy. In vivo acute toxicity studies confirmed the safety of compound 1(a), with no significant alterations observed. To improve the aqueous solubility and pharmacokinetic profile, a mixed micelle-based delivery system by using Pluronics P123 and F127 was developed, and a 2:1 formulation was optimized for demonstrating excellent drug loading (8.8%) and entrapment efficiency (80%). The micellar formulation significantly enhanced the solubility, stability, % growth inhibition, and cellular uptake of 1(a) against MCF-7 and MDA-MB-231 cell lines and intestine permeability. An in vitro drug release study performed at pH 1.2, 6.8, and 7.4 indicated the sustained release behavior of 1(a) . Overall, the results of these experiments supported the potential of Pluronics as a drug delivery system for the potent aromatase inhibitor.