{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:44:30Z","timestamp":1791549870295,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The present study aimed to develop a local dental nanoemulgel formulation of Nigella sativa oil (NSO) for the treatment of periodontal diseases. NSO purchased from a local market was characterized using a GC\u2013MS technique. A nanoemulsion containing NSO was prepared and incorporated into a methylcellulose gel base to develop the nanoemulgel formulation. The developed formulation was optimized using a Box\u2013Behnken statistical design (quadratic model) with 17 runs. The effects of independent factors, such as water, oil, and polymer concentrations, were studied on two dependent responses, pH and viscosity. The optimized formulation was further evaluated for droplet size, drug release, stability, and antimicrobial efficacy. The developed formulation had a pH of 7.37, viscosity of 2343 cp, and droplet size of 342 \u00b1 36.6 nm. Sustained release of the drug from the gel for up to 8 h was observed, which followed Higuchi release kinetics with non-Fickian diffusion. The developed nanoemulgel formulation showed improved antimicrobial activity compared to the plain NSO. Given the increasing emergence of periodontal diseases and antimicrobial resistance, an effective formulation based on a natural antibacterial agent is warranted as a dental therapeutic agent.<\/jats:p>","DOI":"10.3390\/molecules27061796","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:30:38Z","timestamp":1646825438000},"page":"1796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Development and Optimization of Methylcellulose-Based Nanoemulgel Loaded with Nigella sativa Oil for Oral Health Management: Quadratic Model Approach"],"prefix":"10.3390","volume":"27","author":[{"given":"Muhammad H.","family":"Sultan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2145-9956","authenticated-orcid":false,"given":"Shamama","family":"Javed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5139-8408","authenticated-orcid":false,"given":"Osama Ali","family":"Madkhali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9772-0263","authenticated-orcid":false,"given":"Mohammad Intakhab","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-6693","authenticated-orcid":false,"given":"Yosif","family":"Almoshari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ali","family":"Bakkari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durgaramani","family":"Sivadasan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-284X","authenticated-orcid":false,"given":"Ahmad","family":"Salawi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameena","family":"Jabeen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5987-2933","authenticated-orcid":false,"given":"Waquar","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2002). Traditional Medicine Strategy, 2002\u20132005, WHO Publications."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1039\/D1FO00401H","article-title":"Therapeutic perspectives of the black cumin component thymoquinone: A review","volume":"12","author":"Sarkar","year":"2021","journal-title":"Food Funct."},{"key":"ref_3","unstructured":"Indrayan, A.K., Sharma, S., Durgapal, D., Kumar, N., and Kumar, M. (1966). The Wealth of India: A Dictionary of Indian Raw Materials, Publication and Information Directorate, CSIR."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1016\/j.drudis.2021.07.013","article-title":"Thymoquinone: A small molecule from nature with high therapeutic potential","volume":"26","author":"Malik","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.xphs.2017.03.042","article-title":"Recent update on nanoemulgel as topical drug delivery system","volume":"106","author":"Choudhury","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1111\/1440-1681.13553","article-title":"The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases","volume":"48","author":"Soubra","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sallehuddin, N., Nordin, A., Bt Hj Idrus, R., and Fauzi, M.B. (2020). Nigella sativa and Its Active Compound, Thymoquinone, Accelerate Wound Healing in an In Vivo Animal Model: A Comprehensive Review. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17114160"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3906\/vet-1603-26","article-title":"Effects of Nigella sativa and Hypericum perforatum on wound healing","volume":"41","author":"Han","year":"2017","journal-title":"Turk. J. Vet. Anim. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3153\/JFHS18003","article-title":"Nigella sativa oil could induce osteogenic differentiation of dental pulp mesenchymal stem cells: Clinical nutrition for dentistry","volume":"4","author":"Mendi","year":"2018","journal-title":"Food Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2174\/1871529X18666180212114816","article-title":"Immunomodulatory and Anti-inflammatory Effects of Thymoquinone","volume":"18","author":"Noorbakhsh","year":"2018","journal-title":"Cardiovasc. Hematol. Disord. Drug Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.drudis.2008.07.010","article-title":"Recent approaches for the treatment of periodontitis","volume":"13","author":"Jain","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e01495-17","DOI":"10.1128\/AAC.01495-17","article-title":"Evolution of antibiotic resistance without antibiotic exposure","volume":"61","author":"Knoppel","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.15537\/smj.2016.3.13006","article-title":"Nigella sativa and its active constituent thymoquinone in oral health","volume":"37","author":"Zahran","year":"2016","journal-title":"Saudi Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mekhemar, M., Hassan, Y., and D\u00f6rfer, C. (2020). Nigella sativa and thymoquinone: A natural blessing for periodontal therapy. Antioxidants, 9.","DOI":"10.3390\/antiox9121260"},{"key":"ref_15","first-page":"99","article-title":"Effect of Nigella sativa, Salvodora persica (siwak) and aluminium potassium sulphate (Alum) aqueous extract on isolated bacteria from teeth root canal","volume":"9","author":"Ali","year":"2010","journal-title":"Iraqi J. Biotech."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"190342","DOI":"10.1155\/2014\/190342","article-title":"Evaluation of wound closure activity of Nigella sativa, Melastoma malabathricum, Pluchea indica, Piper sarmentosum extracts on scratched monolayer of human gingival fibroblasts","volume":"2014","author":"Rahman","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3892\/mmr.2020.11136","article-title":"Effect of thymoquinone on Fusobacterium nucleatum-associated biofilm and inflammation","volume":"22","author":"Tada","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6645680","DOI":"10.1155\/2021\/6645680","article-title":"HPLC Quantification of Thymoquinone Extracted from Nigella sativa L. (Ranunculaceae) Seeds and Antibacterial Activity of Its Extracts against Bacillus Species","volume":"2021","author":"Habib","year":"2021","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"82","DOI":"10.7324\/JAPS.2015.50915","article-title":"Method development and validation using UV spectrophotometry for Nigella sativa oil microparticles qualification","volume":"5","author":"Ismail","year":"2015","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_20","first-page":"1162","article-title":"Physical stability and antibacterial activity of black cumin oil (Nigella sativa L.) nanoemulsion gel","volume":"4","author":"Jufri","year":"2014","journal-title":"Int. J. Pharm. Technol. Res."},{"key":"ref_21","first-page":"244","article-title":"Emulgel: A novel drug delivery system","volume":"26","author":"Ashara","year":"2016","journal-title":"J. Pak. Assoc. Dermatol."},{"key":"ref_22","first-page":"1488","article-title":"Study of secnidazole- serratiopeptidase alginate\/HPMC gels for periodontal delivery","volume":"3","author":"Priyanka","year":"2011","journal-title":"Int. J. Pharm. Technol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Anantaworasakul, P., Anuchapreeda, S., Yotsawimonwat, S., Naksuriya, O., Lekawanvijit, S., Tovanabutra, N., Anantaworasakul, P., Wattanasri, W., Buranapreecha, N., and Ampasavate, C. (2020). Nanomaterial Lipid-Based Carrier for Non-Invasive Capsaicin Delivery; Manufacturing Scale-Up and Human Irritation Assessment. Molecules, 25.","DOI":"10.3390\/molecules25235575"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jconrel.2003.12.018","article-title":"Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease","volume":"95","author":"Perioli","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liang, J., Peng, X., Zhou, X., Zou, J., and Cheng, L. (2020). Emerging applications of drug delivery systems in oral infectious diseases: Prevention and Treatment. Molecules, 25.","DOI":"10.3390\/molecules25030516"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1600-051X.1992.tb02529.x","article-title":"Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease","volume":"9","author":"Norling","year":"1992","journal-title":"J. Clin. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.jsps.2014.08.002","article-title":"Microemulgel: An overwhelming approach to improve therapeutic action of drug moiety","volume":"24","author":"Ashara","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/ptr.1188","article-title":"Antibacterial activity of medicinal plant extracts against periodontopathic bacteria","volume":"17","author":"Iauk","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1902\/jop.2010.100266","article-title":"Essential oils compared to chlorhexidine with respect to plague and parameters of gingical inflammation: A systematic review","volume":"82","author":"Slot","year":"2011","journal-title":"J. Periodontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.22159\/ijpps.2018v10i7.22966","article-title":"Study of enhanced anti-inflammatory potential of Nigella sativa in topical nanoformulation","volume":"10","author":"Alotaibi","year":"2018","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_31","unstructured":"Ibrahim, S. (2018). Dentifrice Compositions Containing Extracts of Nigella Sativa and Related Methods. (10,004,676), U.S. Patent."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2147\/CCIDE.S140254","article-title":"Acidic oral moisturizers with pH below 6.7 may be harmful to teeth depending on formulation: A short report","volume":"9","author":"Delgado","year":"2017","journal-title":"Clin. Cosmet. Investig. Dent."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Srivastava, N., and Aslam, S. (2021). Recent Advancements and Patents on Buccal Drug Delivery Systems: A Comprehensive Review. Recent Patents Nanotechnol., epub ahead of print.","DOI":"10.2174\/1872210515666210609145144"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1080\/10837450.2020.1753771","article-title":"Mucoadhesive formulations: Innovations, merits, drawbacks, and future outlook","volume":"25","author":"Kumar","year":"2020","journal-title":"Pharm. Dev. Technol."},{"key":"ref_35","first-page":"1726","article-title":"Antibacterial spectrum of black seed oil against selected human pathogenic bacteria","volume":"8","author":"Safhi","year":"2014","journal-title":"J. Pharm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2174\/156720110793566290","article-title":"Local delivery of minocycline hydrochloride: A therapeutic paradigm in periodontal diseases","volume":"7","author":"Javed","year":"2010","journal-title":"Curr. Drug Deliv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2174\/156802662112210906095110","article-title":"Bioactivity of Natural Products as Complementary Medicine","volume":"21","author":"Akkal","year":"2021","journal-title":"Curr. Top. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:48Z","timestamp":1760135628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["molecules27061796"],"URL":"https:\/\/doi.org\/10.3390\/molecules27061796","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,9]]}}}