Paclitaxel-loaded poly(n-butylcyanoacrylate) nanoparticle delivery system to overcome multidrug resistance in ovarian cancer.

Purpose: The aim of this study was to test the ability of paclitaxel-loaded poly(butylcyanoacrylate) (PBCA) nanoparticles to overcome multidrug resistance (MDR) in human ovarian resistant cells (A2780/T) and investigate its possible mechanism.

Methods: We prepared paclitaxel-loaded PBCA nanoparticles by interfacial polymerization method. The physicochemistry of the nanoparticles was characterized. The cytotoxicity of paclitaxel-loaded PBCA nanoparticles was measured by MTT assay. Calcein-AM assay was used to analyze the P-glycoprotein (P-gp) function, and the expression of MDR-1 mRNA in A2780/T cells treated with drug-loaded nanoparticles was defined by QRT-PCR.

Results: The nanoparticles were approximately spherical in shape with an average diameter of 224.5 ± 5.7 nm. The encapsulation efficiency was 99.23%. The in vitro drug release profile exhibited a biphasic pattern. The drug formulated in PBCA nanoparticles showed a greater cytotoxicity than paclitaxel against A2780/T cells. Paclitaxel-loaded PBCA as well as blank PBCA nanoparticles decreased P-gp function in a dose-dependent manner, suggesting the efficacy of the drug-loaded nanoparticle system on overcoming MDR. There was no significant effect on inhibition to the expression of MDR1 mRNA.

Conclusions: Paclitaxel-loaded PBCA nanoparticles can enhance cytotoxicity and overcome MDR through a mechanism of the inhibition of P-gp function caused by the nanoparticles system.