Effect of complexation with randomly methylated beta-cyclodextrin on the aqueous solubility, photostability and antioxidant activity of an indolinonic nitroxide radical.
The interaction between the hydrophobic indolinonic nitroxide radical, 1,2-dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl and hydrophilic alpha-, beta- and gamma-cyclodextrin derivatives was investigated in water by phase-solubility analysis. Among the studied cyclodextrins, random methyl-beta-cyclodextrin (RM-beta-CD) had the greatest solubilizing activity (1312-fold increase in. the intrinsic aqueous solubility). Solid complexes were prepared by the freeze-drying method and characterized by powder X-ray diffractometry and thermal analysis. Complexation of the nitroxide with RM-beta-CD was also confirmed in solution by electron paramagnetic resonance (EPR) spectroscopy. Photodegradation of the nitroxide was reduced by complexation with RM-beta-CD, this effect being more pronounced in the solid-state (the extent of degradation was 28.0% for the complex vs. 78.8% for uncomplexed nitroxide) than in solution (41.2 vs. 69.1% for uncomplexed nitroxide). The antioxidant activity of the complex was also investigated on the peroxidation of methyl linoleate micelles and on protein oxidation induced by free radical generators, and in both systems the free form of the nitroxide as well as its complex with RM-beta-CD, showed essentially the same degree of protection. Moreover, EPR experiments showed a time-dependent decrease in the EPR signal of both the complexed and uncomplexed nitroxides with the free-radical generators. Therefore, RM-beta-CD complexation of the nitroxide represents an effective strategy to improve its aqueous solubility and photostability, which is essential for certain biological applications, while it does not interfere with its radical scavenging efficiency.
Damiani
Elisabetta
E
Istituto di Biochimica, Università Politecnica delle Marche, Via Ranieri, 60131 Ancona, Italy.
Tursilli
Rosanna
R
Casolari
Alberto
A
Astolfi
Paola
P
Greci
Lucedio
L
Scalia
Santo
S
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002621:Chemistry / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006358:Hot Temperature; D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D008027:Light; D008041:Linoleic Acids / Q000737:chemistry; D008745:Methylation; D008956:Models, Chemical; D009589:Nitrogen Oxides / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010777:Photochemistry; D012995:Solubility; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000378:metabolism; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000975:Antioxidants; D005609:Free Radicals; D007211:Indoles; D008041:Linoleic Acids; D009589:Nitrogen Oxides; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D014867:Water; C005575:methyl linoleate; C039900:nitroxyl; D010100:Oxygen