Host–Guest Inclusion Complexes of Essential Oils with Strong Antibacterial and Antifungal Features in Beta-Cyclodextrin for Solid-State Pharmaceutical Applications

Abstract

Essential oils are widely recognized as natural alternatives to pharmaceutical antibacterial and antifungal agents. With respect to standard pharmaceutics, the advantages of essential oils are their (i) low production costs, (ii) lack of chemical and biochemical drawbacks that are intrinsic to the synthetic production process and (iii) good tolerance by humans. On the other hand, the liquid nature of essential oils poses concerns about their actual application in different therapeutic issues regarding their persistence and the ability to control or prolong drug release. In this study, two essential oils from oregano and winter savory showing antibacterial and antifungal features were complexed in a solid state with beta-cyclodextrin. Host–guest inclusion complexes were characterized using FT-IR spectroscopy, ESI-MS and GC-MS techniques. Manyfold terpenic and non-terpenic components of the oils could be observed and unambiguously identified as being included inside the carbohydrate hosts. Many of them provided a specific biocidal action. Indeed, essential oil host–guest inclusion products were tested against two Candida species and an S. aureus reference strain, showing that the oils effectively maintained their liquid performances. Solid-state tablets of the essential oil inclusion complexes embedded in polyvinylpyrrolidone could be obtained. These results pave the way for the solid-state application of essential oils in antibacterial and antifungal pharmaceutical treatments.

Thymus vulgaris Essential Oil in Beta-Cyclodextrin for Solid-State Pharmaceutical Applications

“…Consequently, the molar ratio in the reactive mixture is slightly higher than 1:1 (in favor of the b-CD), potentially also allowing the formation of b-CD:EO 2:1 complexes involving the higher terpenes, however, minor constituents. Moreover, this massive ratio already in the past [ 21 ] with other oils has guaranteed an effective and extensive encapsulation of the substantial totality of the oil, considering that in EOs, the bulk of the formulation is monoterpenes and sesquiterpenes.…”

“…Solid-state Fourier-Transformed (FT) InfraRed (IR) spectra were collected in dry KBr 1-cm pressed (10 tons per square centimeter) discs with a Thermo-Fisher Scientific Nicolet iS50 spectrophotometer (1–3 mg of embedded solid-state samples; for the liquid EO, the surface of a blank KBr disc was impregnated by 1 drop of the essential oil), at 2 cm − 1 spectral resolution of the collected interferogram (100 averaged scansions). This parameter was observed to be appropriate for detecting unambiguously the host–guest complexation peak shifts correlated to the modified intermolecular forces, typically occurring in the 1–15 cm − 1 energy intervals [ 21 , 26 , 27 ].…”

“…The disk diffusion results were statistically analyzed using one-way ANOVA followed by Tukey’s HSD multiple comparisons of means using R (v. 3.5.1) [ 21 ]. Data are presented as boxplots.…”

“…On the contrary, the antimicrobial effect of red thyme has been scarcely reported in the literature [ 18 , 19 , 20 ]. The natural EOs’ antiseptic performances against bacterial and fungal strains mimic those of antibiotics applied in clinical routine [ 15 , 17 , 21 ]. Unfortunately, despite these effective bioactive properties, their oily nature, especially high volatility, and low aqueous solubility pose serious limitations both in their employment as medical devices and in their potential therapeutic application [ 22 ].…”

“…The application of CD and their derivatives in pharmaceutical preparations has a positive impact since they are non-toxic elements with high biocompatibility and solubility in water [ 24 , 25 ]. A successful application of such an approach was the inclusion of oregano and winter savory EOs of in beta-cyclodextrins (b-CD), the most used natural cyclodextrins, obtaining a transfer of the EO liquid components in a solid form [ 21 ].…”