Cutaneous Polymeric-Micelles-Based Hydrogel Containing Origanum vulgare L. Essential Oil: In Vitro Release and Permeation, Angiogenesis, and Safety Profile In Ovo.

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.

Stability Profile and Clinical Evaluation of an Innovative Hydrogel Containing Polymeric Micelles as Drug Delivery Systems with Oregano Essential Oil against Fibroepithelial Polyps.

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50-60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as surgical removal, cauterization, laser irradiation, and cryosurgery. Over-the-counter treatments are also of interest for patients due to their non-invasive character, but their clinical efficiency has not been clearly demonstrated. This study was designed in order to evaluate the efficacy of a modern-pharmaceutical-formulation-type poloxamer-based binary hydrogel, having Origanum vulgare L. essential oil (OEO-PbH) as an active ingredient in the management of FPs. The formulation has been shown to possess good qualities in terms of stability and sterility. Non-invasive measurements revealed changes in some physiological skin parameters. An increase in transepidermal water loss (TEWL) and erythema index was noted, while skin surface water content (SWC) decreased during eight weeks of treatment. The macroscopic evaluation revealed that the FPs dried and shrunk after topical treatment with OEO-PbH. Clinically, patients presented a lowering of the number of lesions on the treated area of 20-30% after one month of treatment and around 50% after the second month. Histopathological examination suggests that topical treatment with OEO-PbH may induce histological changes in the epidermis, dermis, and fibrovascular cores of FPs, including a loss of thickness, reduced size and number of blood vessels, and low cellularity. These changes may contribute to the observed reduction in size of FPs after treatment with OEO-PbH.

Phytochemical Characterization and Biological Evaluation of Origanum vulgare L. Essential Oil Formulated as Polymeric Micelles Drug Delivery Systems.

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.

Study for Evaluation of Hydrogels after the Incorporation of Liposomes Embedded with Caffeic Acid.

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.