Mechanism for Chemical Modification of 2-Hydroxypropyl-β-Cyclodextrin by Pulsed Plasma Irradiation of Liquid Flow

The present work assessed the functionalization of 2-hydroxypropyl-β-cyclodextrin (HPβCD) using a nanosecond pulsed plasma treatment in the liquid phase, at atmospheric pressure, to generate a highly controllable nonequilibrium reaction field. The resulting plasma-activated HPβCD (PA-HPβCD) solutions were evaluated by dynamic light scattering, scanning electron microscopy, and zeta potential measurements. The products generated by the plasma exposure and the associated reaction mechanisms were investigated using nuclear magnetic resonance spectroscopy, liquid chromatography-tandem mass spectrometry, matrix-assisted laser desorption/ionization mass spectrometry, and electron spin resonance spectroscopy. The PA-HPβCD was found to retain the original cyclic backbone structure, although surface hydroxypropyl groups were oxidized, removed, or rearranged, leading to radical processes such as dimerization. In addition, a narrower particle size distribution and reduced dispersion stability were observed following the plasma treatment. These results suggest that plasma exposure could serve as a useful tool for controlling and tuning the functionalization of cyclodextrin for medical applications.