The effect of pharmaceuticals on the nanoscale structure of PEO-PPO-PEO micelles.
We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5wt% F127 solutions were used to measure micelle core size (R(1)), micelle corona size (R(2)), intermicellar interaction distance (R(int)), polydispersity (sigma), and aggregation number (N(agg)); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle-water partition coefficient (K(mw)). The core and corona size were found to generally increase in the presence of the drugs, as did R(int). Both sigma and N(agg) were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on K(mw) in most cases. The aggregation number, however, was found to depend strongly on both K(mw) and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.
Sharma
Praveen K
PK
Department of Chemical Engineering, 159 Goessmann Laboratory, University of Massachusetts, Amherst, MA 01003-9303, USA.
Reilly
Meghan J
MJ
Jones
Deanna N
DN
Robinson
Paul M
PM
Bhatia
Surita R
SR
D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008823:Micelles; D033363:Neutron Diffraction; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D020442:Poloxamer / Q000737:chemistry*; D012107:Research Design; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D008823:Micelles; D004364:Pharmaceutical Preparations; D020442:Poloxamer