Molecular dynamics studies in polymeric micelles using fast field-cycling NMR relaxometry

C. FRAENZA, G. FARRHER, E. ANOARDO, A. ORDIKHANI-SEYEDLAR, C. MATTEA, S. STAPF, R. GLISONI Y A. SOSNIK

Torino

Conferencia; 8th Conference on Field Cycling NMR Relaxometry; 2013

The administration of drugs presenting low solubility in biological fluids still reptresents a crucial biopharmaceutic limitation for the pharmaceutical industry, being the case for about 50% of the approved drugs and 70% of those in the pipeline. Among the existing strategies to overcome this problem, inclusion of hydrophobic drugs into polymeric micelles is one of the most attractive and versatile alternatives. Amphiphilic poly(ethylene oxide)?poly(propylene oxide) block copolymers are thermoresponsive materials that display unique aggregation properties in aqueous medium. Due to their ability to form stable micellar systems in water, these materials are broadly studied for the solubilization of poorly water-soluble drugs. In this work, molecular dynamics of triblock copolymers (commercial name Pluronic block copolymers) F68 (EO80PO27EO80), F108 (EO141PO44EO141), and F127 (EO101PO56EO101) at different concentrations (10-22.5% w/v) and temperatures (3-25°C) were analyzed using fast field-cycling NMR relaxometry. The frequency range was from 8 KHz to 20 MHz, considering that the measured local field values were lower than 1 KHz for all the samples. This study was complemented with NMR spectroscopy, NMR measurements in the rotating frame, atomic force microscopy (AFM), transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Although proton NMR spin-lattice relaxation rate dispersions showed a weak dispersion in the laboratory frame and no dispersion in the rotating frame, they evidenced a bi-exponential behavior that has been attributed to different relaxation of PEO and PPO groups in agreements with other authors [1]. Also, it was observed that the larger the ratio R, defined by number of protons of PPO divided number of protons of PEO, the less evident bi-exponentiality. Efforts will be done in order to explain, using a physical model, this weak dispersion in relaxation times and its bi-exponential behavior. References:  [1] Ma J., Guo C., Tang Y., Xiang J., Chen S., Wang J. Liu H., Journal of Colloid and Interface Science, 2007, 312, 390.