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Keywords = stable ozonides

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18 pages, 3108 KB  
Article
Ozonized Sunflower Oil: Standardization and Mechanisms of the Antimicrobial Effect
by Matheus Henrique Vieira, Diogo Boreski, Bibiana Franzen Matte, Jean Lucas de Oliveira Arias, Celso Martins Júnior, Tais Maria Bauab, Sthefano Atique Gabriel and Chung Man Chin
Int. J. Mol. Sci. 2025, 26(18), 9156; https://doi.org/10.3390/ijms26189156 - 19 Sep 2025
Cited by 7 | Viewed by 3767
Abstract
Ozonized vegetable oils are gaining attention for their antimicrobial and therapeutic potential, yet the lack of standardized ozonation protocols and incomplete characterization of their chemical profiles hinder clinical translation. In this study, we standardized the ozonation process of sunflower oil and investigated the [...] Read more.
Ozonized vegetable oils are gaining attention for their antimicrobial and therapeutic potential, yet the lack of standardized ozonation protocols and incomplete characterization of their chemical profiles hinder clinical translation. In this study, we standardized the ozonation process of sunflower oil and investigated the chemical evolution and antimicrobial efficacy of the resulting products. Ozonation proceeded through a classical three-step mechanism involving the formation of primary ozonides, their decomposition into carbonyl compounds and carbonyl oxides, and subsequent recombination into stable secondary ozonides capable of sustained ozone release with reduced toxicity. Time-course analysis at 100, 240, and 480 min revealed key reaction products, including the appearance of azelaic acid after 240 min, progressive depletion of linoleic acid, and the emergence of 2,5-furandione exclusively after 480 min—indicative of advanced oxidative processes. The formation of hydroperoxides and their secondary degradation into ketones, acids, and epoxides was also observed, with implications for both biological activity and sensory properties. Importantly, the ozonized oil demonstrated potent antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella choleraesuis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus brasiliensis. These findings provide a comprehensive chemical and functional characterization of ozonized sunflower oil and support its development as a standardized antimicrobial agent for therapeutic use. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Ozone Therapy)
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10 pages, 897 KB  
Article
Ozonated Olive Oil Dressing for Pediatric Hypospadias Repair: A Prospective Randomized Clinical Trial
by Vincenzo Coppola, Maria Escolino, Fulvia Del Conte, Claudia Di Mento, Francesca Carraturo, Giovanni Esposito, Francesco Tedesco, Roberta Guglielmini and Ciro Esposito
Children 2025, 12(5), 549; https://doi.org/10.3390/children12050549 - 24 Apr 2025
Cited by 1 | Viewed by 2902
Abstract
Many ozone-based products that promote the healing process of wounds have been released in recent years. In this study, we evaluate a new spray dressing preparation based on stable ozonides with Vitamin E Acetate in children operated for distal hypospadias. Methods: We [...] Read more.
Many ozone-based products that promote the healing process of wounds have been released in recent years. In this study, we evaluate a new spray dressing preparation based on stable ozonides with Vitamin E Acetate in children operated for distal hypospadias. Methods: We included all patients with distal hypospadias, who underwent Tubularized Incised Plate Urethroplasty (TIPU) over a 12-month period. The patients were randomized in two groups according to the type of medication: ozonide spray with Vitamin E Acetate (G1); hyaluronic acid cream (G2). After discharge, parents changed the dressing twice a day for 2–3 weeks postoperatively. The patients were evaluated at 7, 14, 21, 30, 60, and 180 postoperative days and thereafter annually. At the end of the treatment, we submitted a satisfaction questionnaire to parents. Results: Eighty-six patients (median age 18 months) were included. The wound healing was significantly faster in G1 compared with G2 (p = 0.001). No adverse skin reactions occurred in either group. Foreskin dehiscence and re-operation rates were lower in G1. Postoperative foreskin retractability was better in G1, with a significantly higher incidence of secondary phimosis in G2. The median treatment costs were significantly lower in G1 compared with G2 (p = 0.001). Group 1 found the spray dressing easy to use, improving patient management and adherence. Conclusions: The new preparation of ozonide-based product adopted promoted faster wound healing compared to conventional dressing. Furthermore, this spray preparation is easy to apply, economical, and simpler to preserve. This is better for parents who do not have to touch the wound to apply the product. Full article
(This article belongs to the Section Pediatric Surgery)
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11 pages, 1707 KB  
Communication
Characterization of Pure Ozonides from Ozonolysis of Oleic Acid Methyl Ester; Use of a Protocol for the Analysis of the Corresponding Stable Ozonides from Triolein and Organic Extra Virgin Olive Oil (+OIL®)
by Serena Vella, Marina DellaGreca, Angela Tuzi and Flavio Cermola
Molecules 2025, 30(3), 507; https://doi.org/10.3390/molecules30030507 - 23 Jan 2025
Cited by 6 | Viewed by 2604
Abstract
As part of the research directed at establishing the composition of the main products present in Ozoile®, a study of the ozonolysis of the oleic acid methyl ester as well as triolein was undertaken. Starting from oleic acid methyl ester, all [...] Read more.
As part of the research directed at establishing the composition of the main products present in Ozoile®, a study of the ozonolysis of the oleic acid methyl ester as well as triolein was undertaken. Starting from oleic acid methyl ester, all six ozonides were isolated for the first time and fully characterized. Then, we used a protocol based on ozonolysis of triolein and +OIL followed by trans-esterification of the crude reaction mixtures, which led to the same six ozonides. Furthermore, to exclude the formation of any other oxygenated compounds, both during the ozonolysis process and afterward, the reactivity towards 3O2 and 1O2 was explored. The ozonolysis of oleic acid methyl ester in a participating solvent (MeOH) was also investigated. Full article
(This article belongs to the Section Organic Chemistry)
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17 pages, 5740 KB  
Article
Dual-Responsive Alginate/PNIPAM Microspheres Fabricated by Microemulsion-Based Electrospray
by Gianluca Ciarleglio, Monica Placido, Elisa Toto and Maria Gabriella Santonicola
Polymers 2024, 16(19), 2765; https://doi.org/10.3390/polym16192765 - 30 Sep 2024
Cited by 18 | Viewed by 4347
Abstract
Smart materials for drug delivery are designed to offer a precise and controlled release of therapeutic agents. By responding to specific physiological stimuli, such as changes in temperature and pH, these materials improve treatment efficacy and minimize side effects, paving the way for [...] Read more.
Smart materials for drug delivery are designed to offer a precise and controlled release of therapeutic agents. By responding to specific physiological stimuli, such as changes in temperature and pH, these materials improve treatment efficacy and minimize side effects, paving the way for personalized therapeutic solutions. In this study, we present the fabrication of dual-responsive alginate/poly(N-isopropylacrylamide) (PNIPAM) microspheres, having the ability to respond to both pH and temperature variations and embedding the lipophilic bioactive compound Ozoile. Ozoile® Stable Ozonides is obtained from extra virgin olive oil and acts as an inducer, interacting with major biological pathways by means of modulating the systemic redox balance. The dual-responsive microspheres are prepared by electrospray technique without the use of organic solvents. PNIPAM is synthesized by radical polymerization using the APS/TEMED redox initiators. The microspheres are further optimized with a chitosan coating to enhance their stability and modulate the degradation kinetics of the gel matrix. A comprehensive morphological analysis, Fourier transform infrared (FTIR) spectroscopy, and degradation assays are conducted to confirm the structural stability and pH-responsive behavior of the hydrogel microspheres. A study of the volume phase transition temperature (VPTT) by differential scanning calorimetry (DSC) is used to assess the microsphere thermal response. This research introduces a promising methodology for the development of targeted drug delivery systems, which are particularly useful in the context of oxidative stress modulation and inflammation management. Full article
(This article belongs to the Special Issue Smart and Bio-Medical Polymers)
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14 pages, 1893 KB  
Article
Possible Role of NRF2 in Cell Response to OZOILE (Stable Ozonides) in Children Affected by Lichen Sclerosus of Foreskin
by Caterina Saija, Monica Currò, Salvatore Arena, Maria Paola Bertuccio, Fabiola Cassaro, Angela Simona Montalto, Michele Rosario Colonna, Daniela Caccamo, Carmelo Romeo and Pietro Impellizzeri
Curr. Issues Mol. Biol. 2024, 46(9), 9401-9414; https://doi.org/10.3390/cimb46090557 - 26 Aug 2024
Cited by 8 | Viewed by 2891
Abstract
Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children [...] Read more.
Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children affected by LS, reducing the inflammatory process and stimulating tissue regeneration of the foreskin, showing a similar efficacy to steroid treatment. In this study, the modulation of inflammatory and oxidative stress pathways was evaluated by qRT-PCR and Western blotting in foreskins affected by LS removed from patients untreated or treated with OZOILE or corticosteroid cream formulations for 7 days before circumcision. OZOILE induced a significant increase in NRF2 and SOD2 levels, while it did not produce change in MIF, NF-kB subunits, and MMPs in comparison to untreated foreskins. Conversely, steroid topical treatment produced a significant reduction in the expression of p65, MIF, and MMP9, but it did not cause variation in NRF2 and SOD2 levels. These results demonstrate that the use of OZOILE as cream formulation exhibits effects on NRF2 signaling, and it does not induce NF-κB activation, unlike corticosteroids. On the basis of our biochemical data, further studies evaluating the role of NRF2 signaling cascade are necessary. Full article
(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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9 pages, 2458 KB  
Article
Stable Ozonides plus Vitamin E Acetate (Ozoile) for Treatment of Genitourinary Syndrome
by Carlo Ronsini, Irene Iavarone, Natalino Lacerenza, Giada Andreoli, Maria Giovanna Vastarella, Pasquale De Franciscis, Mario Passaro, Raffaella De Simone, Domenico Giraldi, Rosalia Lizza and Giampaolo Mainini
Medicina 2024, 60(6), 880; https://doi.org/10.3390/medicina60060880 - 27 May 2024
Cited by 2 | Viewed by 2669
Abstract
Background and Objectives: Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E [...] Read more.
Background and Objectives: Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E is an important antioxidant diminishing the output of reactive oxygen species in the oxidation of fats and the emanation of free radicals, reducing cellular injury and aging. The primary aim of the present study was to assess the positive effects of an ozonide plus a vitamin E acetate-based compound (Ozoile) on genitourinary syndrome symptom relief after a maximum of 20 days of treatment. Materials and Methods: The inclusion criteria for patients’ enrollment were women of child-bearing age or in menopause reporting genitourinary syndrome’s related symptoms, such as pain, burning, a bad smell, dyspareunia, dryness, itching, bleeding, and nervousness. The exclusion criteria were Sjogren’s syndrome and patients administered retinoic acid, an agent that causes mucosal dryness. Participants completed a questionnaire before and after 20 days of treatment. Results: The incidence of pain decreased from 16.7% to 11.8% (p-value < 0.0001). In addition, the mean symptom intensity decreased from 2.10 to 0.87 (p-value < 0.0001). Dryness was the most frequent pre-treatment symptom and decreased from 85.5% to 53.8% (p-value < 0.0001) (mean: 2.21 vs. 0.90; p-value < 0.0001). Conclusions: Ozoile was effective in reducing most gynecologic symptoms related to genitourinary syndrome. However, further studies are needed to compare its effect with other standards of care. Full article
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16 pages, 4132 KB  
Article
Fabrication of Alginate/Ozoile Gel Microspheres by Electrospray Process
by Gianluca Ciarleglio, Tiziana Russo, Elisa Toto and Maria Gabriella Santonicola
Gels 2024, 10(1), 52; https://doi.org/10.3390/gels10010052 - 11 Jan 2024
Cited by 26 | Viewed by 5136
Abstract
Natural polymers, such as alginate and chitosan, are widely exploited for drug delivery applications due to their biocompatibility, low toxicity, and sustainable sourcing. In this study, pH-responsive gel microspheres were fabricated from an alginate/Ozoile emulsion. Ozoile (Stable Ozonides) is a biological inducer, derived [...] Read more.
Natural polymers, such as alginate and chitosan, are widely exploited for drug delivery applications due to their biocompatibility, low toxicity, and sustainable sourcing. In this study, pH-responsive gel microspheres were fabricated from an alginate/Ozoile emulsion. Ozoile (Stable Ozonides) is a biological inducer, derived from olive oil, which stimulates the endogenous defense system by promoting the repair of tissue damage and restoration of proper physiology through the regulation of gene transcription. Here, the versatile and cost-effective electrospray technique without the use of organic solvents was used to fabricate alginate/Ozoile microspheres with high throughput. The process parameters (voltage, flow rate, and needle gauge) were optimized to obtain microspheres with good sphericity factor and tailored diameter (250–700 μm). The microspheres were additionally optimized through a chitosan coating to enhance their stability and regulate the gel matrix’s degradation process. Morphological analysis, FTIR spectroscopy, and degradation tests confirmed the structural integrity and pH-responsive behavior of the gel microspheres. This research offers a promising route for targeted drug delivery systems, particularly in applications related to the modulation of oxidative stress and management of inflammation. Full article
(This article belongs to the Special Issue Physically Cross-Linked Gels and Their Applications)
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16 pages, 2238 KB  
Article
Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes
by Maria Paola Bertuccio, Valentina Rizzo, Salvatore Arena, Alessandra Trainito, Angela Simona Montalto, Daniela Caccamo, Monica Currò, Carmelo Romeo and Pietro Impellizzeri
Curr. Issues Mol. Biol. 2023, 45(2), 1333-1348; https://doi.org/10.3390/cimb45020087 - 5 Feb 2023
Cited by 17 | Viewed by 4562
Abstract
Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert [...] Read more.
Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert anti-inflammatory effects. However, ozonated oil has been used mainly for topical applications and no data are available about its effects on intestinal cells or immune cells. In this study, we evaluated Ozoile effects on human HT-29 colonic cells and THP-1 monocytic cells stimulated with LPS to induce inflammation. HT-29 and THP-1 cells were treated with LPS in the presence/absence of Ozoile for 4 h. Biomarkers of inflammation, some members of tight junctions and the adhesion molecule ICAM were assessed by qRT-PCR. Protein expression was analyzed by Western blotting. The release of TNF-α and IL-1β was measured by ELISA. In HT-29, Ozoile inhibited LPS-induced expression of TNF-α, IL-1β, ZO-1, CLDN1, NOS2 and MMP-2 and increased the expression of Nrf2 and SOD2 antioxidant proteins. In THP-1 cells, the LPS induction of TNF-α, IL-1β and ICAM was counteracted by Ozoile treatment. Our in vitro results demonstrate the effectiveness of Ozoile in reducing the inflammatory response in intestinal and monocytic cells. Further in vivo studies are necessary to confirm its possible use for intestinal inflammatory conditions. Full article
(This article belongs to the Special Issue Bioactives and Inflammation)
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