Development and optimization of Soluplus®/Pluronic-based polymeric micelles for bicalutamide delivery:...

Polymeric micelles are promising nanocarriers for improving the solubility and therapeutic efficacy of poorly water-soluble drugs. In this study, bicalutamide (BIC)-loaded polymeric micelles were developed and optimized using central composite design (CCD) by varying two formulation factors: the Soluplus® percentage (%) and the Pluronic F127/Pluronic F68 ratio (w/w). The selected formulations exhibited favorable physicochemical properties with particle size (PS) below 100 nm, low polydispersity index (PDI) (≤ 0.066), and high encapsulation efficiencies (EE) (up to 90.6 %). Transmission electron microscopy (TEM) confirmed the spherical and monodisperse structure. The micelles exhibited near-neutral zeta potentials. Lyophilization with trehalose did not significantly alter particle size or uniformity. In vitro release studies demonstrated sustained drug release profiles for 72 h, and in vitro solubility measurements revealed a significant increase (∼161 to 335-fold) compared to free BIC. The formulations also remained colloidally stable upon dilution and were physically stable for up to 6 months at 4 °C, 25 °C/60 % Relative Humidity (RH), and 40 °C/75 % RH. Cellular uptake studies in the human prostate cancer (PC-3) cell line confirmed effective internalization of the micelles. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated a concentration- and time-dependent cytotoxicity. F7 exhibited superior cytotoxicity among the tested formulations, compared to free BIC, while its blank formulation showed no significant toxicity, indicating favorable biocompatibility. These results suggest that the developed polymeric micelle systems have potential as stable and biocompatible delivery systems for BIC, warranting further investigation.