Photosynthesis of hypericin in aqueous medium: A greener approach to prodrug strategy design in photodynamic therapy

In line with environmental concerns, in this study we propose a new protocol to perform the photosynthesis of Hypericin (Hyp) from protohypericin (Protohyp) in aqueous medium. The kinetic parameters of the Protohypto-Hyp photoconversion were investigated in aqueous nanostructured systems formed by the non-polymeric surfactants SDS, CTAB and TX-100 as well as the P-123, F-127 and P-84 copolymers. In all surfactant systems evaluated it was possible to obtain Hyp from the Protohyp irradiation using a low power light source. The kinetic model of pseudo-first order was used for the theoretical fits of kinetic experimental data. Values of kinetic constants (k) in acetone (6.6 ms(-1)) and ethanol (7.8 ms(-1)) were used as references. Highest rate of Protohyp-to-Hyp photoconversion in non-polymeric systems were verified in SDS (k = 21.9 ms(-1)). As for copolymeric systems, the photoreaction happened more quickly in F-127 (k = 6.7 ms(-1)). Concomitantly with kinetic studies, investigations were conducted to evaluate the potential of Protohyp in a prodrug strategy aiming for Hyp. The photoconversion process was investigated in situ in a biological environment composed by Caco-2 intestinal colon carcinoma cells incubated with Protohyp (0.5 mu mol L-1) formulated in P-123, F-127 and P-84 aqueous copolymeric system. The in vitro assays showed photodynamic activity in all systems evaluated, indicating that Hyp has been formed under suitable conditions to trigger the photosensitization process that results in cell death, without requiring the use of organic solvents. (C) 2020 Elsevier B.V. All rights reserved.