Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic® block copolymers

Micelles formed by Pluronic(R) block copolymers (PBC) have been studied in multiple applications as drug delivery systems. Hydrophobic PBC form lamellar aggregates with a higher solubilization capacity than spherical micelles formed by hydrophilic PBC. However, they also have a larger size and low stability. To overcome these limitations, binary mixtures from hydrophobic PBC (L121, L101, L81, and L61) and hydrophilic PBC (F127, P105, F87, P85, and F68) were prepared. In most cases, PBC mixtures were not stable, revealing formation of large aggregates and phase separation within 1-2 day(s). However, stable aqueous dispersions of the particles were obtained upon (1) sonication of the PBC mixtures for 1 or 2 min or (2) heating at 70 degreesC for 30 min. Among all combinations, L121/F127 mixtures (1:1% weight ratio) formed stable dispersions with a small particle size. The solubilizing capacity of this system was examined using a model water-insoluble dye, Sudan (III). Mixed L121/F127 aggregates exhibited approximately 10-fold higher solubilization capacity compared to that of F127 micelles. In conclusion, stable aqueous dispersions of nanoscale size were prepared from mixtures of hydrophobic and hydrophilic PBC by using the external input of energy. The prepared mixed aggregates can efficiently incorporate hydrophobic compounds. (C) 2003 Elsevier B.V. All rights reserved.