A surfactant-stripped cabazitaxel micelle formulation optimized with accelerated storage stability

Area of Science:

• Pharmaceutics
• Drug Delivery
• Nanotechnology

Background:

• Cabazitaxel (CTX) is a second-generation taxane with limited aqueous solubility, posing formulation challenges.
• Pluronic (Poloxomer) micelles offer a potential solution for solubilizing hydrophobic drugs like CTX.
• Stabilized, surfactant-stripped cabazitaxel (sss-CTX) micelles resist aggregation and offer higher drug-to-surfactant ratios.

Purpose of the Study:

• To investigate the impact of elevated temperatures on sss-CTX micelle aggregation for formulation optimization.
• To develop and characterize an sss-CTX micelle formulation using mifepristone as a co-loader.
• To evaluate the in vitro and in vivo performance of the sss-CTX formulation compared to conventional micelle formulations.

Main Methods:

• Micelle formulation using Pluronic (Poloxomer) and co-loading with mifepristone.
• Surfactant-stripping technique to enhance drug-to-surfactant ratio.
• In vitro studies: drug release, hemolysis, complement activation, microtubule stabilization, cytotoxicity.
• In vivo studies: pharmacokinetics and therapeutic efficacy in Lewis lung carcinoma and malignant pleural effusion models.

Main Results:

• Elevated temperatures accelerate sss-CTX micelle aggregation, aiding formulation optimization.
• A stable sss-CTX formulation with mifepristone (60% mass ratio) was successfully developed.
• In vitro and in vivo studies showed comparable drug release, hemolysis, complement activation, microtubule stabilization, cytotoxicity, pharmacokinetics, and therapeutic efficacy to conventional Tween-80 formulations.
• The sss-CTX formulation achieved a substantially higher drug-to-surfactant ratio and demonstrated extended aqueous storage stability.

Conclusions:

• Stabilized, surfactant-stripped cabazitaxel (sss-CTX) micelles provide a promising alternative to conventional formulations.
• The sss-CTX formulation offers enhanced drug-to-surfactant ratios and improved aqueous storage stability.
• This approach holds potential for improved delivery and efficacy of cabazitaxel and other hydrophobic drugs.