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Semifluorinated block copolymers of oligo(ethylene glycol) methacrylate (OEGMA) and 1H,1H,2H,2H-perfluorooctyl methacrylate (FOMA) were prepared using group transfer polymerization via sequential monomer addition. Wide ranges of copolymers were obtained with good control over both molecular weight and composition by adjusting the monomer/initiator ratio. Analogous statistical copolymers were prepared using radical polymerization in supercritical CO2. The micelle-like aggregates of the block copolymers in water and chloroform were characterized by quasi-elastic light scattering and transmission electron microscopy. The size and morphology of the aggregates were found to depend on the nature of solvent, temperature, and the copolymer composition. The solubility of copolymers and the formation of hydrated reverse micelles in CO2 were investigated. The block copolymer showed a better ability of solubilizing water in CO2 than the statistical copolymer.

Titanium dioxide nanoparticles were produced by the controlled hydrolysis of titanium tetraisopropoxide (TTIP) in the presence of reverse micelles formed in CO2 with the surfactants ammonium carboxylate perfluoropolyether (PFPECOO^-+NH4) (Mw = 587) and poly(dimethyl amino ethyl methacrylate-block-1H,1H,2H,2H-perfluorooctyl methacrylate) (PDMAEMA-b-PFOMA). Based on dynamic light scattering measurements, the amorphous TiO2 particles formed by injection of TTIP are larger than the reverse micelles, indicating surfactant reorganization. The size of the particles and the stability of dispersions in CO2 were affected by the molar ratio of water to surfactant headgroup (wo), precursor concentration, and injection rate. The amorphous particle size did not change upon depressurization and redispersion in CO2. PDMAEMA-b-PFOMA provided greater stability against particle aggregation at higher reactant concentration compared with PFPECOO^-+NH4. The crystallite size after calcination, which was examined by X-ray diffraction and transmission electron microscopy, increased with wo.

Silica colloids were sterically stabilized in supercritical CO2 by end-grafting poly(1H,1H-dihydroperfluorooctyl methacrylate) (PFOMA) onto the particle surfaces. Turbidity versus time measurements were used to determine the CO2 density below which the colloids flocculated, that is, the critical flocculation density (CFD). The CFD was determined as a function of stabilizer molecular weight and temperature as the solvent density was lowered. All of the CFDs occurred above the upper critical solution density for the corresponding finite-molecular-weight stabilizer in bulk CO2 and corresponded more closely with the estimated Θ density. The CFDs decreased (reflecting greater stability) when temperature was increased or the PFOMA molecular weight was decreased. The latter result suggests that, at lower solvent densities, the shorter chains experience better solvation and, hence, provide greater steric repulsion than the longer chains. For the stabilizers of highest molecular weight, the colloids become unstable slightly above the Θ density, possibly as a result of chain contraction from long-range van der Waals forces with the particle surface.

We report nonflocculated dilute water-in-CO2 (W/C) miniemulsions stable for 24 h in contrast with flocculated unstable macroemulsions reported previously. The surfactants, poly(1,1-dihydroperfluorooctyl methacrylate)-b-poly(ethylene oxide) (PFOMA-b-PEO), were synthesized by atom transfer radical polymerization to achieve the proper hydrophilic−CO2-philic balance (HCB) and a low interfacial tension (~0.2−2 mN/m) between water and CO2. The average particle diameter, ranging from 70 to 140 nm, was measured with multiwavelength turbidimetry utilizing Mie theory, and the interfacial tension was measured with high pressure pendant drop tensiometry. Because flocculation and coalescence were suppressed nearly completely, it became feasible to investigate emulsion droplet formation and droplet growth by Ostwald ripening. Droplet formation was characterized as a function of the mechanical energy at various CO2 densities and temperatures and was correlated quantitatively to the interfacial tensions. The molar water/surfactant ratios reached 1170, in contrast with values of only about 5−60 for W/C microemulsions. The ability to stabilize nanometer-sized miniemulsion droplets with large water/surfactant ratios is of great practical interest in reactions, separations, and materials formation processes in CO2.

Although the ability of chemosensitizers to modulate P-glycoprotein (PGP)-based multidrug resistance (MDR) has been extensively studied, relatively little is known about the cellular pharmacology of the PGP inhibitors themselves in MDR cells. The studies described here have correlated the in vitro accumulation and retention properties of verapamil (VRP) in murine P388 (sensitive) and P388/ADR (MDR) cells with doxorubicin (DOX) uptake and cytotoxicity modulation characteristics in order to better understand VRP-tumor cell interactions that give rise to MDR modulation. VRP is rapidly taken up by DOX-sensitive and -resistant P388 cells where greater than 50% maximal VRP uptake occurs within 10 min of initial exposure at 37°C. Whereas chemosensitization and DOX uptake in P388/ADR cells increase with increasing VRP concentration until a plateau is achieved at approximately 5 μM VRP, cellular modulator levels increase proportionally with increasing VPR concentrations beyond 20 μM. Subsequent to removal of noncell-associated modulator, VRP levels in both sensitive and resistant cells rapidly fall below 10% of those obtained at uptake equilibrium. However, a residual amount of VRP remains associated with the cells for extended time periods after the cells are washed. Pulse exposures of P388/ADR cells to high concentrations of VRP (50-100 μM) are capable of providing extended cell-associated VRP levels comparable to those obtained with continuous exposure at biologically active VRP concentrations (1-3 μM) and this leads to chemosensitization. These results are consistent with the existence of high- and low-affinity intracellular VRP pools in P388 MDR cells, both of which can contribute to the reversal of drug resistance. It is suggested that these properties should be taken into consideration during the design and evaluation of preclinical in vivo MDR models where pulsed exposure to high concentrations of resistance modulators often occurs. Special attention must be given to whether such high concentration pulses are desirable and/or achievable in relevant clinical settings.

Trifunctional poly(dimethylsiloxane) (PDMS) block copolymers PDMS-b-poly(tert-butyl acrylate (tBA)-co-acrylic acid (AA)), PDMS-b-poly(methyl methacrylate), PMMA-b-PAA, and PDMS-b-P(MMA-co-methyacrylic acid (MA)) were synthesized and utilized to stabilize PMMA latexes in both nonpolar (CO2) and polar (water) solvents. Submicron PMMA particles synthesized by dispersion polymerization in supercritical CO2 have been redispersed to form up to 40 wt % stable aqueous latexes. In CO2, the PDMS block provides steric stabilization. Upon transfer to water, the MA or AA groups ionize producing electrostatic stabilization, while the acrylate group anchors to the PMMA polymer surface. In both media, the particle size remained constant, indicating good stabilization without agglomeration. The surfactant is “ambidextrous” in that stabilization is achieved in both CO2 and water and by different mechanisms in each medium. PMMA particles stabilized with a PDMS macromonomer could be transferred to an aqueous solution of sodium dodecyl sulfate in water to produce a stable latex.