Paclitaxel and Tacrolimus Coencapsulated Polymeric Micelles That Enhance the Therapeutic Effect of Drug-Resistant Ovarian Cancer

摘要

The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating multidrug resistance in tumors has attracted increasing attention. However, the poor water solubility of some anticancer drugs restricted their clinical application. In this work, we prepared poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles as a codelivery system to load the chemotherapy drug paclitaxel (PTX) and the multidrug-resistant reversing agent tacrolimus (FK506). The PTX- and FK506-coloaded MPEG-PCL micelles (P-F/M) were prepared by a one-step solid dispersion method without any surfactants, toxic organic solvent, or severe experimental conditions. P-F/M had small particle size (28.7 +/- 3.2 nm) and high encapsulation efficiency (99.3 +/- 0.5%). Compared with A2780s cells (PTX-sensitive human ovarian cancer cells), P-F/M showed a stronger cytotoxicity and an improving intracellular drug concentration of PTX than PTX-loaded micelles (PTX/M) in A2780/T cells (PTX-resistant human ovarian cancer cells). Furthermore, a P-F/M codelivery system showed a more significant G(2)/M arrest and apoptosis induction effects, as well as activating apoptosis protein signaling pathway, in A2780/T cells than in A2780s cells. In summary, the results suggested that the codelivery micelles of PTX and FK506 may serve as a potential candidates against MDR human ovarian cancer.