{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:09:52Z","timestamp":1768075792024,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP-2021\/146"],"award-info":[{"award-number":["RSP-2021\/146"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We develop a suitable delivery system for niaouli essential oil (NEO) using a nanoemulsification method for acne vulgaris. Prepared nanoemulsions (NEs) were characterized for droplet dimension, rheology, surface charge, and stability. The ability of NEO formulations against Propionibacterium acnes and Staphylococcus epidermidis was investigated and all formulations showed antiacne potential in vitro. Ex vivo permeation studies indicated significant improvement in drug permeations and steady state flux of all NEO-NEs compared to the neat NEO (p &lt; 0.05). On the basis of the studied pharmaceutical parameters, enhanced ex vivo skin permeation, and marked effect on acne pathogens, formulation NEO-NE4 was found to be the best (oil (NEO; 10% v\/v); Kolliphor EL (9.25% v\/v), Carbitol (27.75% v\/v), and water (53% v\/v)). Concisely, the in vitro and ex vivo results revealed that nanoemulsification improved the delivery as well as bioactivities of NEO significantly.<\/jats:p>","DOI":"10.3390\/molecules26164750","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T21:43:53Z","timestamp":1628199833000},"page":"4750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nanoemulsification Improves the Pharmaceutical Properties and Bioactivities of Niaouli Essential Oil (Melaleuca quinquenervia L.)"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-0885","authenticated-orcid":false,"given":"Faiyaz","family":"Shakeel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-137X","authenticated-orcid":false,"given":"Mounir M.","family":"Salem-Bekhit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazrul","family":"Haq","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-9819","authenticated-orcid":false,"given":"Sultan","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.tifs.2021.01.070","article-title":"Recent updates on the chemistry, bioactivities, mode of action, and industrial applications of plant essential oils","volume":"110","author":"Ni","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shameen, J.B., Mahomoodally, F.M., Zengin, G., and Maggi, F. (2021). Essential oils as natural sources of fragrance compounds for cosmetics and cosmeceuticals. Molecules, 26.","DOI":"10.3390\/molecules26030666"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1071\/CH9682585","article-title":"The steam-volatile constituents of Melaleuca viridiflora Sol. ex Gaertn","volume":"21","author":"Hellyer","year":"1968","journal-title":"Aust. J. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4103\/0974-8490.210329","article-title":"Investigation of the effect of 1,8-cineole on antimicrobial activity of chlorhexidine gluconate","volume":"9","author":"Simsek","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36548","DOI":"10.1021\/acsami.7b09067","article-title":"Investigation of antibacterial 1,8-cineole-derived thin films formed via plasma-enhanced chemical vapor deposition","volume":"9","author":"Mann","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0169-409X(00)00103-4","article-title":"Microemulsion based media as novel drug delivery systems","volume":"45","author":"Lawrence","year":"2000","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/10717544.2013.843610","article-title":"Comparative topical delivery of croconazole using liposome and micro-emulsion-based gel formulations","volume":"21","author":"Fetih","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.2217\/nnm-2020-0079","article-title":"Design and development of a commercially potential in situ nanoemulgel for the treatment of postmenopausal osteoporosis","volume":"15","author":"Zakir","year":"2020","journal-title":"Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.1002\/slct.201902007","article-title":"Enhanced skin permeation of hydrocortisone using nanoemulsion as potential vehicle","volume":"4","author":"Altamimi","year":"2019","journal-title":"ChemistrySelect"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E82","DOI":"10.1007\/s13205-019-1630-y","article-title":"Wound healing evaluation of self-nanoemulsifying drug delivery system containing Piper cubeba essential oil","volume":"9","author":"Shakeel","year":"2019","journal-title":"3 Biotech."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpharm.2019.05.061","article-title":"Solidified SNEDDS for the oral delivery of rifampicin: Evaluation, proof of concept, in vivo kinetics, and in silico GastroPlusTM simulation","volume":"566","author":"Hussain","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_12","first-page":"13","article-title":"Characterization and in vitro bioactive studies of lemongrass oil phytonanoemulsion system in the treatment of acne vulgaris","volume":"3","author":"Faiyazuddin","year":"2009","journal-title":"Int. J. Essen. Oil Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105206","DOI":"10.1039\/C5RA22900F","article-title":"Biological evaluation of a supersaturated self-nanoemulsifying drug delivery system of Piper cubeba essential oil","volume":"5","author":"Shakeel","year":"2015","journal-title":"RSC Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3109\/21691401.2016.1163716","article-title":"Wound healing effects of nanoemulsion containing clove essential oil","volume":"45","author":"Alam","year":"2017","journal-title":"Art Cells Nanomed. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"957","DOI":"10.5650\/jos.ess18005","article-title":"Wound healing study of eucalyptus essential oil containing nanoemulsion in rat model","volume":"67","author":"Alam","year":"2018","journal-title":"J. Oleo Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0962-4562(02)00034-6","article-title":"Aetiology and management of acne vulgaris","volume":"12","author":"Bensouilah","year":"2002","journal-title":"Int. J. Aromather."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.sder.2005.03.004","article-title":"The role of inflammation in the pathogenesis of acne and acne scarring","volume":"24","author":"Holland","year":"2005","journal-title":"Sem. Cut. Med. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S1773-2247(06)50090-5","article-title":"Niaouli oils as enhancer for transdermal permeation of estradiol evaluation of gel formulations on hairless rats in vivo","volume":"16","author":"Monti","year":"2006","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/10717540902896297","article-title":"Niaouli oils from different sources: Analysis and influence on cutaneous permeation of estradiol in vitro","volume":"16","author":"Monti","year":"2009","journal-title":"Drug Deliv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1023\/A:1021129710316","article-title":"The fungicidal activity of novel nanoemulsion (X8W60PC) against clinically important yeast and filamentous fungi","volume":"155","author":"Myc","year":"2001","journal-title":"Mycopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11046-013-9622-7","article-title":"Antifungal activity of nanocapsule suspensions containing tea tree oil on the growth of Tricophyton rubrum","volume":"175","author":"Flores","year":"2013","journal-title":"Mycopathologia"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Muta, T., Parikh, A., Kathawala, K., Haidari, H., Song, Y., Thomas, J., and Garg, S. (2020). Quality-by-design approach for the development of tea tree oil formulation-impregnated biocompatible gel with antimicrobial properties. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111091"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E104999","DOI":"10.1016\/j.yrtph.2021.104999","article-title":"Characterization of tea tree oil nanoemulsion and its acute and subchronic toxicity","volume":"124","author":"Wei","year":"2021","journal-title":"Reg. Toxicol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E13678","DOI":"10.1038\/s41598-019-50134-y","article-title":"Enrichment of eucalyptus oil nanoemulsion by micellar nanotechnology: Transdermal analgesic activity using hot plate test in rats\u2019 assay","volume":"9","author":"Aziz","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.2147\/IJN.S252640","article-title":"Preparation of celery essential oil-based nanoemulsion by ultrasonication and evaluation of its potential anticancer and antibacterial activity","volume":"15","author":"Nirmala","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejpb.2016.11.018","article-title":"Hydrogel-thickened nanoemulsions based on essential oils for topical delivery of psoralen: Permeation and stability studies","volume":"116","author":"Barradas","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"626","DOI":"10.12944\/CRNFSJ.6.3.05","article-title":"Essential oil nanoemulsions and theier antimicrobial and food applications","volume":"6","author":"Pathania","year":"2018","journal-title":"Curr. Res. Nutr. Food Sci."},{"key":"ref_28","first-page":"348","article-title":"Production, characterization, in vitro and ex vivo studies of babchi oil-encapsulated nanostructure solid lipid carriers produced by a hot aqueous titration method","volume":"65","author":"Faiyazuddin","year":"2010","journal-title":"Pharmazie"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Davarani, F.H., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejpb.2006.10.014","article-title":"Development and bioavailability assessment of ramipril nanoemulsion formulation","volume":"66","author":"Shafiq","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0378-5173(94)00222-Q","article-title":"An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy","volume":"114","author":"Craig","year":"1995","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0378-5173(98)00092-1","article-title":"Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN\u2122) dispersions","volume":"68","author":"Freitas","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.colsurfb.2009.09.010","article-title":"Trnasdermal delivery of anticancer drug caffeine from water-in-oil nanoemulsions","volume":"75","author":"Shakeel","year":"2010","journal-title":"Coll. Surface B."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"573","DOI":"10.3109\/10717544.2013.868557","article-title":"Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-flourouracil: A preliminary study","volume":"22","author":"Shakeel","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.56808\/3027-7922.2194","article-title":"Stability evaluation of celecoxib nanoemulsion containing Tween 80","volume":"32","author":"Shakeel","year":"2008","journal-title":"Thai J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.3797\/scipharm.1210-02","article-title":"Accelerated stability testing of a clobetasol propionate-loaded nanoemulsion as per ICH guidelines","volume":"81","author":"Ali","year":"2013","journal-title":"Sci. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4314\/tjpr.v14i1.3","article-title":"Stability testing of beclamethasone dipropionate nanoemulsion","volume":"14","author":"Alam","year":"2015","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2133.1984.tb04664.x","article-title":"Comparison of topical clindamycin phosphate, benzoyl peroxide, and a combination of the two for the treatment of acne vulgaris","volume":"110","author":"Tucker","year":"1984","journal-title":"Br. J. Dermatol."},{"key":"ref_39","first-page":"208","article-title":"Formulation and evaluation of an effective pH balanced topical antimicrobial product containing tea tree oil","volume":"60","author":"Biju","year":"2005","journal-title":"Pharmazie"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/4750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:17Z","timestamp":1760164877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/4750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,5]]},"references-count":39,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["molecules26164750"],"URL":"https:\/\/doi.org\/10.3390\/molecules26164750","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,5]]}}}