Formulation, Optimization, and Evaluation of Oregano Oil Nanoemulsions for the Treatment of Infections Due to Oral Microbiota

Khaled Hosny,1– 3 Hani Asfour,4 Waleed Rizg,1– 3 Nabil A Alhakamy,1– 3 Amal Sindi,5 Hala Alkhalidi,6 Walaa Abualsunun,1 Rana Bakhaidar,1 Alshaimaa M Almehmady,1 Sara Akeel,5 Sarah Ali,5 Adel Alghaith,7 Sultan Alshehri,7 Rasha Khallaf8 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Oral diagnostic sciences department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Clinical pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62511, EgyptCorrespondence: Khaled HosnyDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaTel +966 561682377Email elswaify2000@yahoo.com; kmhomar@kau.edu.saIntroduction: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation’s aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health.Methods: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities.Results: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats.Conclusion: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.Keywords: oregano essential oil, nanoemulsion, Box‒Behnken design, ulcer index, required HLB, carvacrol, thymol, stability index