Exemestane

Exemestane, an aromatase inhibitor used in breast cancer, demonstrated antiproliferative effects in non-small cell lung cancer (NSCLC) cell lines H23 and A549. Both cell lines expressed aromatase, with A549 showing higher levels than H23. Exemestane reduced cell proliferation and increased apoptosis in a dose-dependent manner, with A549 being more sensitive. In A549 cells, exemestane did not alter aromatase protein or mRNA levels. In H23 cells, exemestane increased both aromatase expression and cAMP levels. Exemestane also induced EGFR activation and translocation from the cell membrane in H23 cells but not in A549 cells. These findings suggest that exemestane may have therapeutic potential in NSCLC, particularly in tumors with higher aromatase expression. The differential effects on EGFR signaling between cell lines indicate that combination therapy with EGFR inhibitors might be more effective in certain NSCLC subtypes.

Fig. 1 Schematic illustration of the potential mechanisms of Mazdutide. (Koutras A.; et al. 2019)

Exemestane (EXE), a BCS Class IV breast cancer drug with poor solubility and low oral absorption, was formulated into a thermoresponsive lamellar liquid crystal gel for topical delivery. SAXS confirmed a lamellar structure with a lattice parameter of ~15 nm, which expanded with increasing oil and EXE due to hydrophobic interactions. Rheology showed gel-like behavior at low shear and room temperature, converting to a Newtonian liquid at higher shear rates and above 37°C. Drug release was 38% at 37°C and increased to 50% at 42°C over 24 hours. This formulation offers enhanced solubility, permeability, and hyperthermia-induced drug release, avoiding hepatic metabolism and reducing systemic side effects.

Fig. 2 Thermoresponsive liquid crystalline formulation of Exemestane. (Shah V.; et al. 2021)