Current development of cabazitaxel drug delivery systems

Abstract

The second-generation taxane cabazitaxel has been clinically approved for the treatment of metastatic castration-resistant prostate cancer after docetaxel failure. Compared with the first-generation taxanes paclitaxel and docetaxel, cabazitaxel has potent anticancer activity and is less prone to drug resistance due to its lower affinity for the P-gp efflux pump. The relatively high hydrophobicity of cabazitaxel and the poor aqueous colloidal stability of the commercial formulation, following its preparation for injection, presents opportunities for new cabazitaxel formulations with improved features. This review provides an overview of cabazitaxel drug formulations and hydrophobic taxane drug delivery systems in general, and particularly focuses on emerging cabazitaxel delivery systems discovered in the past 5 years.

Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis

“…36,37 To enhance the water solubility, bioavailability, and reduce toxicity of taxanes, various pharmaceutical formulation techniques such as liposomes, polymeric micelles, and other carriers have been developed as nanomedicine delivery systems. [38][39][40] Building upon the synergistic anti-tumor effect of NO and PTX and with the goal of improving the pharmacokinetic prole of PTX, we previously designed and synthesized an NO-donating polymer, consisting of monomethoxy poly(ethylene glycol) and polylactic acid (mPEG-PLA-NO). This polymer was used to generate biodegradable polymeric micelles loaded with PTX (NO/ PTX) in a nanoparticle delivery system (Fig.…”

A novel cabazitaxel liposomes modified with ginsenoside Rk1 for cancer targeted therapy

“…In contrast to the CTX-Sol and Chol/CTX-Lip groups, the number of bone marrownucleated cells in the Rk1/CTX-Lip group did not differ from that in the saline group (Figure 4D and Table 3). As a highlighted concern in the clinical application of CTX therapies, hematotoxicity has become the focus of safety inspection [31,32] . Rk1/CTX-Lip exhibited robust in vivo protection against hematological toxicity.…”

Reduction-Responsive Stearyl Alcohol-Cabazitaxel Prodrug Nanoassemblies for Cancer Chemotherapy

“…Unfortunately, the present therapeutic outcomes of chemotherapy based on taxane derivatives still fall short of expectations due to severe systemic toxicities and multidrug resistance [ 3 , 4 ]. As a new generation of semisynthetic taxane derivative, cabazitaxel (CTX) shows a lower affinity for P-glycoprotein and superior antitumor efficacy, holding great potential for the treatment of docetaxel-resistant metastatic breast cancer [ 5 ]. However, the present clinical formulation (e.g., Jevtana ® ) added a large amount of Tween 80 and ethanol to overcome the poor solubility of CTX, resulting in further excipient-associated toxicities, such as allergic reactions, anemia, hepatotoxicity and neurotoxicity [ 6 ].…”