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Ind. Eng. Chem. Res. 2009, 48, 1928–1932
Block Copolymer Micelles Formed in Supercritical Fluid Can Become Water-Dispensable Nanoparticles: Poly(ethylene glycol)-block-Poly(E-caprolactone) in Trifluoromethane Zachary Tyrrell, Winoto Winoto, Youqing Shen, and Maciej Radosz* Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, UniVersity of Wyoming, Laramie, Wyoming 82071-3295
Micelles of hydrophilic-hydrophobic block polymers, such as poly(ethylene glycol)-block-poly(-caprolactone) (PEG-b-PCL), used as drug-delivery carriers, are generally fabricated via solvent displacement or dialysis, which is time-consuming, requires freeze drying, and can leave toxic traces of the residual organic solvents. An alternative is presented in this paper: form micellar PEG-b-PCL nanoparticles in a supercritical fluid solvent and then disperse them in water toward a water-dispensable formulation. This method is illustrated with pressure-temperature phase diagrams for PEG-b-PCL in supercritical trifluoromethane, which is selective enough for the PCL and PEG blocks to induce micellization. When subjected to decompression to remove trifluoromethane, dry and organic solvent-free nanoparticles are readily obtained. Their micellar structure is immediately reestablished in water, as confirmed by laser light scattering. Neither has been demonstrated previously. Introduction Block copolymers are potential delivery vehicles for hydrophobic drugs, especially those for cancer therapy.1-6,11 Of specific interest are polymers that are able to self-assemble into nanosized precursor micelles in an aqueous solution. Several block copolymer compositions, such as triblock copolymers of ethylene oxide and propylene oxide (PEO-b-PPO-b-PEO), Pluronics), are approved for use in pharmaceutical formulations.7 However, they exhibit low drug loading capacity and low stability upon dilution (for example, when injected into the bloodstream).7 Polymers that contain blocks with higher hydrophobicity, such as poly(ethylene glycol)-b-poly(-caprolactone) (PEG-b-PCL), have been shown to improve both drug loading capacity and stability.8 The downside to PEG-b-PCL, however, is that micelle formation cannot be achieved by simply dissolving the polymer in water, because this copolymer is insoluble in water in its virgin disordered state. The conventional micelle preparation method is a solvent displacement or dialysis method, in which the polymer is first dissolved in a water-miscible organic solvent and then the solution is either added dropwise to or dialyzed against water for nanoparticle formation and removal of the organic solvent. The dilute nanoparticle solution (generally
