Nur Sena Basarir1,2, Jenny Lam2, Hanan Fael1, Ayca Yildiz Pekoz1
1Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul/Türkiye
2University College London, School of Pharmacy, Department of Pharmaceutics, London/UK
Summary
The homeostatic mechanism that occurs during cholesterol synthesis is known to become impaired in some cancer cases, such as non-small cell lung cancer (NSCLC), and result in a free circulating lipid buildup in the tumor microenvironment. Statins have been shown to be effective in reducing this lipid buildup and exhibit a dual effect independent of their cholesterol-lowering mechanism, which could be related to their anticancer properties. This project aimed to formulate a carrier-free dry powder for inhalation of simvastatin. One significant aspect of the study is that the active pharmaceutical ingredient (API) itself is a prodrug and is not pharmacologically active unless it undergoes the hepatic first-pass mechanism. Since, with inhalation, the lungs are targeted directly and would not be subjected to this mechanism, we had to ensure that the biological activity of the formulation would be enhanced. Characterization studies such as particle size distribution, scanning electron microscopy (SEM) imaging, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were carried out. Cell culture studies were also performed with MTT and Western Blotting assays to show the effect of the formulation on cancerous cell lines A549, Calu-3 and H1975.
Gary.Basarir