Role of Unimers to Polymersomes Transition in Pluronic Blends for Controlled and Designated Drug Conveyance

This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (η<inf>rel</inf>) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (ΔG°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.