Effect of anti-inflammatories on Pluronic F127: micellar assembly, gelation and partitioning

We present results on the effect of two anti-inflammatory agents, naproxen and indomethacin, on the structure, assembly and gelation transitions of Pluronic F127 micelles. Small-angle neutron scattering experiments on micellar solutions indicate that the micelle aggregation number decreases significantly in the presence of drug solutes, causing the number density of micelles to increase. However, only slight changes were observed in the critical micelle concentration of F127 in the presence of these drugs. Both anti-inflammatory agents were found to shift the liquid-to-gel and gel-to-liquid transitions of the copolymer to lower temperatures. This may be the result of an increase in the micellar volume fraction, caused by the presence of the hydrophobic drugs. Using an ultraviolet spectroscopy technique, we have also measured the solubilities and micelle-water partition coefficients (Kmw) of naproxen and indomethacin in water and F127 solutions. The values of Kmw for naproxen and indomethacin are 355 +/- 64 and 474 +/- 33, respectively. They are larger than previously reported lipid-water partition coefficients, indicating that F127 micelles may be a better choice for drug loading than lipid vesicles. The slightly greater effects of indomethacin on the gelation boundary as compared with naproxen may be attributable to a higher value of Kmw.