Inhalable Nano Formulation of Cabazitaxel: A Comparative Study with Intravenous Route.

Abstract

Chemotherapy is generally given by intravenous (IV) administration which provides higher bioavailability than other systemic routes. However, in the case of lung cancer, the pulmonary (INH) route is the other choice for inhalable formulations. In the study, biochemical and histological parameters of Cabazitaxel (CBZ) free (2 mg kg^-1) and nanoparticle (NP) (2 mg kg^-1 CBZ equivalent) formulations are investigated after IV and INH administration in rats. The nanoformulation of CBZ is obtained using PEGylated polystyrene (PEG-PST) nanoparticles obtained by PISA. While a nose and head-only device is used for INH administration, a jugular vein is used as the IV route. Blood samples (blank, 24 h, and 48 h) are collected via carotid artery cannulas without handling in metabolism cages. According to biochemical parameters, free CBZ formulation applied via IV or INH route shows higher systemic toxicity. On the other hand, the nanoformulation of CBZ showed no signs of toxicity in both IV or INH routes. Higher and longer retention is observed in the case of inhaled nanoformulation. Histological analysis showed higher alveolar macrophage migration for inhaled nanoformulation due to enhanced retention. Results showed that nanotechnology and the lung defense system gave the advantage to end up with an inhalable nanomedicine formulation for lung cancer.