New repurposed rolapitant in nanovesicular systems for lung cancer treatment: Development, in-vitro assessment and in-vivo biodistribution study.

ABSTRACT

Lung cancer is characterized by poor prognosis, and is considered a serious disease that causes a significant mortality. The available conventional chemotherapeutic agents suffer from several limitations; hence, new drug molecules are constantly being sought. In the current study, lipid nanovesicles (LNVs) were selected as a colloidal vehicle for encapsulation of the FDA-approved drug; rolapitant (RP), which is used particularly for the treatment of nausea and vomiting, but is repurposed for the treatment of lung cancer in the current work. RP was loaded into various LNVs (liposomes, ethosomes and transethosomes) using the thin film hydration method, and the LNVs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), storage stability and surface morphology. Besides, the in-vitro drug release, in-vitro cytotoxicity on A549 lung cancer cells, nebulization performance using next generation impactor (NGI), and the in-vivo biodistribution behavior were evaluated. The selected ethosomal and transethosomal vesicles displayed a particle size less than 400 nm, a positive charge, and EE% exceeding 90% for RP, with a sustained release pattern over 15 days. The in-vivo biodistribution results proved the high lung deposition potential of RP-LNVs with a considerable safety. Besides, the developed RP-LNVs were able to reach the metastatic organs of lung cancer, hence they were proven promising as a possible treatment modality for lung cancer.