Effect of the Surfactant Charge on the Characteristics and Anticancer Effects of Docetaxel-loaded Poloxamer Polymeric Micelles

Abstract

Background: The main problem in the use of docetaxel as a potent chemotherapeutic agent is its solubility. Practically insoluble docetaxel requires a harsh formulation with high surfactant and alcohol concentrations to comply with the product quality. However, this formulation is inconvenient for patients. Polymeric micelles using a biocompatible polymer, poloxamer, seem to be a promising approach to increase the solubility of docetaxel, avoiding the high polysorbate and alcohol contents in the commercial product and yielding similar or better anticancer effects.

Objective: This study aims to investigate the effects of surfactant with three different charges on the particle size, chemical stability, in vitro drug release and anticancer efficacy of the docetaxelloaded poloxamer-based polymeric micelle formulation.

Methods: The freeze drying method was used to prepare polymeric micelles of docetaxel. Dynamic light scattering was used to determine particle size. The morphology of particles was investigated using a transmission electron microscope. High Pressure Liquid Chromatography was used to measure encapsulation efficiency, drug loading, and percentage of drug released. MTT assay was used to assess the anticancer effect.

Results: Nonionic and anionic surfactants tended to increase the particle size, while cationic surfactants had no effect. Furthermore, the addition of cationic surfactant increased the chemical stability of docetaxel. Poloxamer polymeric micelles have sustained drug release, and the addition of a surfactant can increase polymeric micelle drug release. All surfactant charges increased the anticancer efficacy of docetaxel compared to the commercial formulation Taxotere, except for the formulation prepared with an anionic surfactant.

Conclusion: The charge of the surfactant affects the particle size, chemical stability, drug release and anticancer properties of docetaxel-loaded poloxamer polymeric micelles. Cationic surfactant formulations have shown to be promising, resulting in the most stable and highest anticancer effect.

Keywords: Docetaxel; anticancer effect; cyclophosphamide; poloxamer; polymeric micelle; surfactant.