IN VITRO ANTIVIRAL EVALUATION OF NEW DELIVERY SYSTEMS WITH NAPHTHOQUINONE DERIVATIVE
DENV; dengue; naphthoquinones; IVS320; cyclodextrins; inclusion complexes; drug delivery systems; pharmaceutical technology
The outbreak of dengue fever, a disease transmitted by the DENV virus, has spread globally, causing
millions of deaths worldwide. Therefore, it is necessary to develop new compounds that can act in the
treatment of dengue fever. Naphthoquinones (NQs) and their derivatives have antifungal, antiparasitic
and antimicrobial action, among which is the compound IVS320, a molecule with promising
antimicrobial action, but with low solubility. Cyclodextrins (CDs) are used as a strategy to improve the
solubility, stability and bioavailability of drugs. In this context, the development of inclusion
complexes (ICs) with cyclodextrins can solve the implicit restrictions of IVS320, and in turn, increase
its bioavailability and pharmacological action. Thus, the present study aims to improve the
physicochemical and biological properties of naphthoquinone IVS320, through the development of
inclusion complexes. In addition to evaluating the in vitro anti-DENV activity of the obtained delivery
systems and analyzing the bioactive potential of the compound, the complexes obtained with γ-CD,
HP-γ-CD and HP-β-CD, through the physical mixing ( MF), kneading (ML) and rotary evaporation
(RT) techniques, were characterized by XRD, FTIR, DSC and TG techniques. The XRD results of the
isolated IVS320 exhibited crystalline reflections with high intensity at 10°, 18°, 32° and 37°, while the
diffractograms of the MF, ML and RT systems showed a reduction in the crystalline profile,
suggesting the formation of complexes . The FTIR spectra of the systems bands showed characteristic
of both IVS320 and the CDs employed, with modifications in the profile of some bands. In turn, the
DSC showed little similarity with the endothermic and exothermic events observed in the isolated
IVS320, and the IC exhibited the main occurrences in the ranges of 70-80°C, 190-200°C, up to
exothermic peaks in the range of 250°C-260°C, signaling crystallization. While in the TG, well
defined stages of mass loss were observed for all complexation techniques, in which the first events of
the systems occurred around 50°C to 70°C, with approximately 10% mass loss, while the second
variation began between 300 and 340°C, followed by gradual mass decay up to 600°C, with the
highest ∆m (approximately 80%). Regarding in vitro activity, the compound IVS320 presented quite
satisfactory results, being able to inhibit the DENV virus. The results of the physicochemical
characterization indicated the formation of IVS320 ICs with CDs, demonstrating that the methods
employed were effective and that the systems developed are promising for enhancing the antiviral
activity of IVS320.