Characterization and application of mixed micellar assemblies of PEO-PPO star block copolymers for solubilization of hydrophobic anticancer drug and in vitro release

Abstract

Over the past few decades, polymeric micelles have attracted enormous attention due to their beneficial properties such as (i) core-shell structure, capable to accommodate hydrophobic drugs, boosting the overall solubility in aqueous medium; (ii) appropriate size which favors accumulation within the tumor, displaying improved permeability and retention (EPR) effect and (iii) unimers that tune the activity of efflux pumps engaged in multidrug resistance (MDR). Taking this into consideration, the present study aims the optimization and application of mixed copolymeric system of polyethylene oxide-polypropylene oxide (PEO-PPO) star block copolymers, Tetronics® 901 and 904 (hereafter written as T901 and T904), with almost same molecular weight of PPO blocks but distinct PEO block lengths, for the solubilization and in vitro release of hydrophobic anticancer drug, curcumin (CN). The copolymer T901 being incorporated with a long PPO block (10% PEO, M. Wt. 4700) is highly unstable and has poor water solubility at ambient temperature. Thus, undergoes phase separation at temperatures below 25 °C. Tetronic® T904 (40% PEO, M. Wt. 6700) with relatively longer PEO blocks forms stable core-shell micelles (hydrodynamic diameter, Dh ~ 12.0 nm and aggregation number, Nagg ~ 24) in water. The inclusion of copolymer T901 in the micellar system of T904 is mutually beneficial for both the copolymers as the insertion of T901 in T904 extends its PPO core and consequently improves its drug solubilizing capacity. On the other hand, the solubility of T901, which otherwise remains insoluble in water (at ambient temperature) is increased. Hence, the assemblies so formed are more efficient for drug delivery and improve the carrier properties of both the copolymers. The solubility and release profiles of drug was also checked in the presence of commonly used pharmaceutical excipients viz. sodium chloride (NaCl) and glucose in isotonic conditions and it was witnessed that the presence of both the excipients promoted micellization and augmented the solubilization capacity of the mixed assemblies many folds. The in-vitro release profiles suggested release of drug through diffusion from the mixed assemblies.