Background: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous
biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels
are a new technology with great potential, which are designated as drug delivery systems. Biphasic
bigels consisting of solid and liquid components represent suitable formulations improving diffusion
and bioavailability of NQs into the skin.
Objective: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone
(M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity
towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application.
Methods: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using
the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel
organogel with sweet almond oil as the non-polar solvent and span 65 as an organogelator.
Their rheological behavior and microscopic properties were characterized. The diffusion kinetics
and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz
cell” in vitro permeation model.
Results: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen
bonds with LYS233 were observed for M1, M2, and phosphoramidon (positive control). The
average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon.
M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and
M2 were cytotoxic towards COLO38 cells (IC50 value: 2.6 and 9.8 μM). The M1 release from
bigels was faster and more efficient than that of M2.
Conclusion: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel
bigels are efficient and safe formulations to overcome their low bioavailability.