Naifa Alenazi, Zenat Khired, Hussam M Shubaily, Yehia Hazzazi, Mohammed Somailie, Abdullah Ali Alamri, Amani Alhejely, Hassien M Alnashiri, Mari Sumayli, Salama A Salama
Letrozole (LTZ), an aromatase inhibitor, is commonly prescribed to patients with breast cancer (BC). LTZ can induce apoptosis and inhibit tumor angiogenesis. Despite its high efficacy, LTZ is hindered by significant side effects, low bioavailability, and poor solubility, all of which limit its overall effectiveness. The aim of this study was to develop a transdermal formulation of LTZ-loaded transbilosomes (LLT) for treatment of BC. This new formulation can lessen LTZ's toxicity while increasing its solubility, targeting, and efficacy. Multiple LLT formulations were created and tested using Design Expert software to select the optimal one. A DMBA rat model was used to evaluate the efficacy, targeting, and safety of the optimal LLT formulation. The optimal LLT formulation decreased drug release by 69.25%, compared to free LTZ. Compared to the disease group, the tumor volume in the transdermal LLT group decreased by 97.65%. The transdermal LLT formulation increased LTZ accumulation in the tumor by 4.7-fold. Histopathological and toxicity studies confirm the antiproliferative effects and safety of the transdermal LLT formulation. These findings support the potential of transdermal LLT formulation to be an effective and safe treatment for BC.