{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:14:27Z","timestamp":1790709267189,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research (DSR) at King Ab-dulaziz University (KAU), Jeddah, Saudi Arabia","award":["RG-44-166-43"],"award-info":[{"award-number":["RG-44-166-43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The foremost target of the current work was to formulate and optimize a novel bergamot essential oil (BEO) loaded nano-phytosomes (NPs) and then combine it with spironolactone (SP) in order to clinically compare the efficiency of both formulations against acne vulgaris. The BEO-loaded NPs formulations were fabricated by the thin-film hydration and optimized by 32 factorial design. NPs\u2019 assessments were conducted by measuring entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In addition, the selected BEO-NPs formulation was further combined with SP and then examined for morphology employing transmission electron microscopy and three months storage stability. Both BEO-loaded NPs selected formula and its combination with SP (BEO-NPs-SP) were investigated clinically for their effect against acne vulgaris after an appropriate in silico study. The optimum BEO-NPs-SP showed PS of 300.40 \u00b1 22.56 nm, PDI of 0.571 \u00b1 0.16, EE% of 87.89 \u00b1 4.14%, and an acceptable ZP value of \u221229.7 \u00b1 1.54 mV. Molecular modeling simulations showed the beneficial role of BEO constituents as supportive\/connecting platforms for favored anchoring of SP on the Phosphatidylcholine (PC) interface. Clinical studies revealed significant improvement in the therapeutic response of BEO-loaded NPs that were combined with SP over BEO-NPs alone. In conclusion, the results proved the ability to utilize NPs as a successful nanovesicle for topical BEO delivery as well as the superior synergistic effect when combined with SP in combating acne vulgaris.<\/jats:p>","DOI":"10.3390\/ph16010128","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T01:31:15Z","timestamp":1673832675000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Exploring the Synergistic Effect of Bergamot Essential Oil with Spironolactone Loaded Nano-Phytosomes for Treatment of Acne Vulgaris: In Vitro Optimization, In Silico Studies, and Clinical Evaluation"],"prefix":"10.3390","volume":"16","author":[{"given":"Rofida","family":"Albash","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3823-5804","authenticated-orcid":false,"given":"Noha M.","family":"Badawi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Cairo 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed I. A.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-8575","authenticated-orcid":false,"given":"Maha H.","family":"Ragaie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, STD\u2019s and Andrology, Faculty of Medicine, Minia University, Al-Minya 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar S.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Dermatology, STD\u2019s and Andrology, Faculty of Medicine, Minia University, Al-Minya 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rovan M.","family":"Elbesh","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy for Women\u2019s Health, Faculty of Physical Therapy, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-482X","authenticated-orcid":false,"given":"Khaled M.","family":"Darwish","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-6243","authenticated-orcid":false,"given":"Manar O.","family":"Lashkar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-0581","authenticated-orcid":false,"given":"Sameh S.","family":"Elhady","sequence":"additional","affiliation":[{"name":"Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Mosallam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121309","DOI":"10.1016\/j.ijpharm.2021.121309","article-title":"Quercetin loaded cosm-nutraceutical electrospun composite nanofibers for acne alleviation: Preparation, characterization and experimental clinical appraisal","volume":"612","author":"Amer","year":"2021","journal-title":"Int. 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