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To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg\/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2\u20138 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 \u00b5g\/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment.<\/jats:p>","DOI":"10.3390\/gels11050373","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:10:46Z","timestamp":1747721446000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design of a Foam-Actuated Nano-Emulgel for Perioceutic Drug Delivery: Formulation, Characterization, and Antimicrobial Efficacy"],"prefix":"10.3390","volume":"11","author":[{"given":"Theresa P. K.","family":"Varughese","sequence":"first","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-155X","authenticated-orcid":false,"given":"Poornima","family":"Ramburrun","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-9977","authenticated-orcid":false,"given":"Nnamdi I.","family":"Okafor","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-1845","authenticated-orcid":false,"given":"Sandy van","family":"Vuuren","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1529","authenticated-orcid":false,"given":"Yahya E.","family":"Choonara","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"},{"name":"Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/prd.12447","article-title":"Risk factors for periodontitis & peri-implantitis","volume":"90","author":"Darby","year":"2022","journal-title":"Periodontology 2000"},{"key":"ref_2","first-page":"72","article-title":"Prevalence of periodontal disease, its association with systemic diseases and prevention","volume":"11","author":"Nazir","year":"2017","journal-title":"Int. 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