Solubility of Fullerenes in Fatty Acids Esters: A New Way to Deliver In Vivo Fullerenes. Theoretical Calculations and Experimental Results
The biological effects of fullerenes and, in particular, of C60 have been recognized since long time. One of the problems which hindered the application of fullerenes in medicinal chemistry regards their insolubility in water and water-based fluids. In the present chapter it is reported that C60 and C70 fullerenes are soluble in vegetable oils, in general, in esters of fatty acids and in free fatty acids. These results pave the way in the utilization of vegetable oils as vehicles in the delivery of fullerenes for both topical applications and internal use (e.g., intramuscular injection).
It is shown that the solubility of fullerenes in vegetable oils can be predicted and justified on the basis of the solubility parameters of C60 and C70 and of the glycerol esters of fatty acids. A detailed procedure for the calculation of the solubility parameters of fullerenes and vegetable oils by group increment is reported.
The solubility of C60 and C70 in a series of vegetable oils, namely: olive, sunflower, peanut, soybean, linseed and castor oil, has been determined quantitatively spectrophotometrically. Additionally, the solubility of C60 and C70 has been determined quantitatively in the methyl esters of brassica oilseed and only qualitatively in molten cow butter, molten stearic acid and molten behenamide. The experimental results show that the solubility of fullerenes appears to be dependent on the unsaturation level of the fatty acids composing the vegetable oils being lower in oils with higher unsaturation level. The solubility has been found dependent also on the polarizability parameter of the vegetable oils.
The stability of C60 and C70 solutions in vegetable oils has been studied in air and under inert atmosphere, after thermal processing and under the action of UV radiation. In all cases it has been found that C60 and C70 are prone to form adducts with the fatty acid chains of the vegetable oils. The adducts are formed both by radical and Diels-Alder mechanisms. The pharmaceutical valency and potential of such adducts has also been discussed.
KeywordsAdducts C60 C70 esters of fatty acid excipients fatty acids fullerenes glycerol esters of fatty acids grafting group increment method solubility solubility parameter vehicles for drug delivery vegetable oils triglycerides
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