Systematic characterization of Pluronic micelles and their application for solubilization and in vitro release of some hydrophobic anticancer drugs

The utilization of polymeric micelles in oncology in the last few decades has progressed by leaps and bounds from the advances in polymer chemistry, in drug formulation and delivery (in vitro and in vivo biological models). Commercially available linear (A-B-A type) ethylene oxide-propylene oxide (EO-PO) block copolymers, Pluronics have acquired added attention by virtue of their capability to load therapeutics, execute the delivery of the consignment to the site of action, improve the pharmacokinetics of the loaded drugs and reduce off-target cytotoxicity. The size of the hydrophobic (middle) and hydrophilic (end) blocks in copolymermolecule plays a decisive role for the drug loading capabilities. Hence, with this objective, we have examined the role of six different Pluronics with varying molecular characteristics in the solubilization of three widely used hydrophobic anticancer drugs genistein (GEN), paclitaxel (PCL), and quercetin (QCT). Stable micelles (apparent hydrodynamic diameter-15-20nm) form in case of moderately hydrophobic copolymers viz. P103 and P123 at ambient temperature while very hydrophilic F88 forms micelles at elevated temperatures due to much higher critical micelle temperature (CMT). All the three drugs showed enhanced solubility in copolymer micelles with the increase in temperature and salt concentration. The drug loading, stability and in vitro release profiles from the micelles were examined using reversed phase HPLC Release profile demonstrated slower and sustained release. The in vitro cytotoxicity of the drug loaded micelles was investigated on MCF-7 breast cancer cells which showed higher anticancer activity as compared to free drugs. PCL loaded P123 micelles exhibited the best anticancer activity. The results of the current work will be highly commodious for the application of Pluronics in anticancer therapeutics. (C) 2017 Elsevier B.V. All rights reserved.