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.

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates.

Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid-N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)-were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC50 values that ranged from 5.7 to 19.6 µM was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC50 = 5.7 µM) and BA2 (IC50 = 10.0 µM) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13-16 µg/mL and 26-32 µg/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 µg/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

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.

Oxidative Stability and Protective Effect of the Mixture between Helianthus annuus L. and Oenothera biennis L. Oils on 3D Tissue Models of Skin Irritation and Phototoxicity.

The present study was aimed to evaluate the oxidative stability as well as to assess the protective effect of the mixture of Helianthus annuus L. (HAO) and Oenothera biennis L. (OBO) oils on 3D tissue models of skin irritation and phototoxicity. The following methods were used: GS analysis (fatty acids composition), thiobarbituric acid-reactive substances assay (TBA) (lipid oxidation degree of tested samples), 3D EpiDerm models (skin irritation and phototoxicity). For HAO the detected saturated fatty acids (SFA) were palmitic acid (7.179%), stearic acid (3.586%), eicosanoic (0.138%) and docosanoic acid (0.548%) The monounsaturated acids (MUFA) were palmitoleic acid (0.158%) and oleic acid (28.249%) and the polyunsaturated acids (PUFA) were linoleic acid (59.941%) and linolenic acid (0.208%). For OBO the detected SFA were myristic acid (0.325%), pentadecylic acid (0.281%), palmitic (7.2%), stearic (2.88%), and arachidic acid (0.275%). Regarding MUFA, even a lower proportion (8.196%) was observed, predominantly being oleic acid, cis form (7.175%), oleic (n10) (0.558%) and 11-eicosenoic (0.210%) acids. The higher content was found for PUFA (82.247%), the most significant proportions being linoleic acid (72.093%), arachidonic acid (9.812%) and linolenic (0.233%). Obtained data indicate a good oxidative stability and biocompatibility of the mixture on the 3D EpiDerm models with no irritant and no phototoxic effects. Oenothera biennis L. oil may be an excellent natural choice in order to delay or prevent oxidative damage of Helianthus annuus L. oil.

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment.

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells-MCF7 and lung carcinoma epithelial cells-A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.