Cabazitaxel-nano delivery systems as a cutting-edge for cancer therapy

Cabazitaxel (CTX), a second-generation taxane, has shown more anticancer efficacy in both docetaxel and paclitaxel-resistance cancer models according to the in vivo experiments. Moreover, Cabazitaxel has a high ability to penetrate the blood-brain compared to paclitaxel for treating brain tumors. The first USFDA-approved formulation of CTX is Jevtana® used for treating hormone-refractory prostate cancer in 2010 after drug resistance occurred against docetaxel therapy. Jevtana uses Polysorbate-80 as a surfactant and ethanol as a co-solvent to enhance the soluble properties of CTX. Polysorbate-80 can cause hydrolysis, so although CTX is used clinically, its application has some limitations for example its solubility and tumor cell uptake are low. Hence, various nanocarriers for CTX have been investigated to overcome these limitations. The main goal is to achieve compelling benefits over Jevtana and other paclitaxel and docetaxel formulations, included improving anticancer efficacy and reducing toxicity. Jevtana needs two individual dilutions before administration. Moreover, it is steady for a short time after being prepared for administration, so novel nanoformulations could be developed to overcome these issues. Nanoparticles based on albumin and lipids, prodrugs, and polymeric nanoparticles have been used as Cabazitaxel carriers in CTX-based chemotherapy in combination with immunotherapy, phototherapy, or gene therapy based on siRNA. As well as, various chemical modification methods have been used to functionalize the carriers and enhance CTX therapy such as acid-sensitive, active targeting, and PEGylation.