Polymeric micelles using cholinium-based ionic liquids for the encapsulation and release of hydrophobic drug molecules

We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic (R) L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The partitioning of the hydrophobic model compound curcumin (CCM) into the PM-rich phase and the drug delivery capabilities of the PMs were investigated. ATPMSs formed using more hydrophobic ILs (i.e., {[}Ch]{[}Hex] approximate to {[}Ch]{[}But] > {[}Ch]{[}Pro] > {[}Ch]{[}Ac] approximate to {[}Ch]Cl) were the most effective in partitioning (K-CCM) and recovering (RECRich) CCM into the PM-rich phase (15.2 < K-CCM < 22.0 and 90% < RECRich < 95%, respectively). Moreover, using 1.2 M {[}Ch]{[}But] and 0.2 M {[}Ch]{[}Hex] ILs yielded higher encapsulation efficiency (EE) (94.1 and 96.0%, respectively) and drug loading (DL) capacity (14.8 and 16.2%, respectively), together with an increase in the average hydrodynamic diameter of the PMs (D-H) (42.5 and 45.6 nm, respectively). The CCM-PM formulations were stable at 4.0, 25.0, and 37.0 degrees C and the release of CCM was faster with the less hydrophobic ILs (i.e., {[}Ch]Cl and {[}Ch]{[}Ac]). Furthermore, due to the lower critical solution temperature properties of Pluronic (R) L35, the PMs exhibit temperature responsiveness at 37.0 degrees C. In vitro cytotoxicity assays were also performed to determine the potency of CCM-PM formulations, and a 1.8-fold decrease in IC50 values was observed between the CCM-PMs/{[}Ch]{[}Hex] and CCM-PMs/{[}Ch]Cl formulations for PC3 cells. The lower IC50 value for the {[}Ch]{[}Hex] version corresponded to a greater potency compared to the {[}Ch]Cl version, since a lower concentration of CCM was required to achieve the same therapeutic effect. The ATPMSs investigated in this study serve as a novel platform for Pluronic (R) L35/PBS buffer (pH 7.4) + IL-based ATPMS development. The unique properties reported here may be useful in applications such as controlled-release drug delivery systems (DDS), encapsulation, and bioseparations. (AU)