Origanum vulgare L. is a widely used aromatic plant, especially due to its content in essential oil, mainly rich in carvacrol and thymol. The ethnopharmacological uses of Origanum vulgare L. essential oil (OEO) comprise digestive, respiratory, or dermatological disorders. The review focuses on the increasing number of recent studies investigating several biological activities of OEO. The bioactivities are in tight relation to the phytochemical profile of the essential oil, and also depend on taxonomic, climatic, and geographical characteristics of the plant material. The antibacterial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antitumor, skin disorders beneficial effects, next to antihyperglycemic and anti-Alzheimer activities were reported and confirmed in multiple studies. Moreover, recent studies indicate a positive impact on skin disorders of OEO formulated as nanocarrier systems in order to improve its bioavailability and, thus, enhancing its therapeutic benefits. The review brings an up to date regarding the phytochemistry and bioactivity of Origanum vulgare L. essential oil, underlining also the most successful pharmaceutical formulation used for skin disorders.

Caffeic acid (CA), a phenolic acid, is a powerful antioxidant with proven effectiveness. CA instability gives it limited use, so encapsulation in polymeric nanomaterials has been used to solve the problem but also to obtain topical hydrogel formulas. Two different formulas of caffeic acid liposomes were incorporated into three different formulas of carbopol-based hydrogels. A Franz diffusion cell system was used to evaluate the release of CA from hydrogels. For the viscoelastic measurements of the hydrogels, the equilibrium flow test was used. The dynamic tests were examined at rest by three oscillating tests: the amplitude test, the frequency test and the flow and recovery test. These carbopol gels have a high elasticity at flow stress even at very low polymer concentrations. In the analysis of the texture, the increase of the polymer concentration from 0.5% to 1% determined a linear increase of the values of the textural parameters for hydrogels. The textural properties of 1% carbopol-based hydrogels were slightly affected by the addition of liposomal vesicle dispersion and the firmness and shear work increased with increasing carbomer concentration.

To initiate our research into the development of biocompatiîle gelled-microemulsions based on essential oils (EOs) and sucrose esters (SEs) for the topical delivery of fluconazole, this formulation study investigated the usefulness of two relatively harmless natural non-ionic surfactants from the group of SEs (sucrose laurate and stearate) to form, in the presence of antifungal EOs, stable, isotropic microemulsions effective on fluconazole solubilization. Fluconazole’s solubility in EO significantly depended on their chemical composition, showing higher values for cinnamon, oregano and clove essential oils, further selected as oil phase components for microemulsion formulations. The phase behavior of several EO–isopropyl miristate/SE–isopropanol/water systems was assessed through pseudo-ternary phase diagrams constructed by microplate dilution technique. The hydrocarbon chain length of the SE and EO type strongly influenced the size of the microemulsion region in the pseudo-ternary phase diagrams. Ten microemulsion formulations containing 2% fluconazole, 6% or 10% oil mixture of EO–isopropyl myristate in 1:1 ratio, 45% SE-isopropanol mixture and water, were selected and evaluated for physicochemical properties (droplet size, polydispersity, viscosity, refractive index, zeta potential and pH). All formulations were physicochemically acceptable, but viscosity enhancement and further in vitro and in vivo tests are required for the development of biocompatible, clinically safe and effective fluconazole topical preparations.

Biocompatible gel microemulsions containing natural origin excipients are promising nanocarrier systems for the safe and effective topical application of hydrophobic drugs, including antifungals. Recently, to improve fluconazole skin permeation, tolerability and therapeutic efficacy, we developed topical biocompatible microemulsions based on cinnamon, oregano or clove essential oil (CIN, ORG or CLV) as the oil phase and sucrose laurate (D1216) or sucrose palmitate (D1616) as surfactants, excipients also possessing intrinsic antifungal activity. To follow up this research, this study aimed to improve the adhesiveness of respective fluconazole microemulsions using chitosan (a biopolymer with intrinsic antifungal activity) as gellator and to evaluate the formulation variables’ effect (composition and concentration of essential oil, sucrose ester structure) on the gel microemulsions’ (MEGELs) properties. All MEGELs were evaluated for drug content, pH, rheological behavior, viscosity, spreadability, in vitro drug release and skin permeation and antifungal activity. The results showed that formulation variables determined distinctive changes in the MEGELs’ properties, which were nevertheless in accordance with official requirements for semisolid preparations. The highest flux and release rate values and large diameters of the fungal growth inhibition zone were produced by formulations MEGEL-FZ-D1616-CIN 10%, MEGEL-FZ-D1216-CIN 10% and MEGEL-FZ-D1616-ORG 10%. In conclusion, these MEGELs were demonstrated to be effective platforms for fluconazole topical delivery.

This study presents phytochemical characterization and biological evaluation of Origanum vulgare L. essential oil (OEO) formulated as polymeric micelles drug delivery systems as a possible non-invasive approach for the management of skin tags. GC-MS analysis of Romanian OEO revealed the identification and quantification of 43 volatile compounds (thymol and carvacrol being the main ones). The antioxidant activity was shown by four consecrated methods: CUPRAC, ABTS, ORAC and DPPH. OEO was incorporated by micellar solubilization into a binary hydrogel based on a Pluronic F 127/L 31 block-copolymers mixture. The pH, consistency, spreadability, particle size, polydispersity index and zeta potential of the OEO-loaded poloxamer-based binary hydrogel (OEO-PbH) were investigated. OEO-PbH was skin compatible in terms of pH and exhibited adequate spreadability and consistency. The minimal inhibitory concentrations of the tested OEO were similar to those obtained for the formulation, lower (2.5 µg/mL) for yeast and higher (40–80 µg/mL) for Gram-negative bacilli. As keratinocytes are among main components of skin tags, an in vitro evaluation was conducted in order to see the effect of the formulation against HaCaT human keratinocytes. OEO-PbH decreased HaCaT cells migration and proliferation and elicited a cytotoxic and pro-apoptotic effect in a dose- and time-dependent manner. No harmful effect on the viability of dendritic cells (DCs) was detected following the incubation with different concentrations (0–200 µg/mL) of the 5% formulation. Treatment in inflammatory DCs (+LPS) indicated a decrease in cytokine production of IL-6, TNF-α and IL-23 but no significant effect on IL-10 in any of the tested concentrations.

Origanum vulgare var. vulgare essential oil (OEO) is known as a natural product with multiple beneficial effects with application in dermatology. Oregano essential oil represents a potential natural therapeutic alternative for fibroepithelial polyps (FPs), commonly known as skin tags. Innovative formulations have been developed to improve the bioavailability and stability of essential oils. In this study, we aimed to evaluate the morphology of a polymeric-micelles-based hydrogel (OEO-PbH), the release and permeation profile of oregano essential oil, as well as to assess in vivo the potential effects on the degree of biocompatibility and the impact on angiogenesis in ovo, using a chick chorioallantoic membrane (CAM). Scanning electron microscopy (SEM) analysis indicated a regular aspect after the encapsulation process, while in vitro release studies showed a sustained release of the essential oil. None of the tested samples induced any irritation on the CAM and the limitation of the angiogenic process was noted. OEO-PbH, with a sustained release of OEO, potentially enhances the anti-angiogenic effect while being well tolerated and non-irritative by the vascularized CAM, especially on the blood vessels (BVs) in the presence of leptin treatment. This is the first evidence of in vivo antiangiogenic effects of a polymeric-micelle-loaded oregano essential oil, with further mechanistic insights for OEO-PbH formulation, involving leptin as a possible target. The findings suggest that the OEO-containing polymeric micelle hydrogel represents a potential future approach in the pathology of cutaneous FP and other angiogenesis-related conditions.