An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis

Abstract

Periodontitis is a chronic bacterial infection, and its effective treatment is dependent on the retention of antibiotics of effective concentrations at the periodontal pockets. In this study, a solution-gel based inverse lyotropic liquid crystalline (LLC) system was explored to deliver metronidazole to the periodontal pockets for local treatment of periodontitis. It was found that the metronidazole-loaded LLC precursor spontaneously transformed into gel in the presence of water in the oral cavity. The low viscosity of the precursor would allow its penetration to the rather difficult to reach infection sites, while the adhesiveness and crystalline nanostructures (inverse bicontinuous cubic Pn3m phase and inverse hexagonal phase) of the formed gel would permit its firm adhesion to the periodontal pockets. The LLC system provided sustained drug release over one week in vitro. Results from in vivo study using a rabbit periodontitis model showed that the LLC system was able to maintain the metronidazole concentrations in the periodontal pockets above the minimum inhibition concentration for over 10 days without detectable drug concentration in the blood. Owing to the spontaneous solution-gel transition in the periodontal pockets and unique liquid crystalline nanostructures, the LLC in situ gel provided effective treatment of periodontitis for a prolonged period of time with reduced systematic side effects, compared to metronidazole suspension which was effective for 24 h with detectable metronidazole concentrations in the blood after 6 h.

Current Knowledge Regarding the Interaction Between Oral Bone Metabolic Disorders and Diabetes Mellitus

“…Therefore, careful consideration is still recommended before administering antibiotics. Anaerobic and facultative anaerobes are the main pathogens causing periodontal infection, and the local application of nitroimidazole drugs has a therapeutic effect in chronic periodontitis (136). Previous studies have reported that supportive treatment with prophylactic antibiotics and mouthwash improves implant survival and reduces postoperative complications (78).…”

Smart phase transformation system based on lyotropic liquid crystalline@hard capsules for sustained release of hydrophilic and hydrophobic drugs

“…Lyotropic liquid crystalline (LLC) is self-assembled nanostructured gel that can be formed by amphiphilic lipids and surfactant in aqueous environment (Wang et al, 2019). It has multiple crystal structures, that is, lamellar, cubic and hexagonal (Qian et al, 2015;Mei et al, 2017a). The special structures provide incorporation of drugs with different solubility, including hydrophilic, hydrophobic and amphiphilic molecules (Conn & Drummond, 2013;Rajabalaya et al, 2017) and also tunable release rate (Rizwan & Boyd, 2015;Abd-Allah et al, 2016;Huang & Gui, 2018).…”

“…The special structures provide incorporation of drugs with different solubility, including hydrophilic, hydrophobic and amphiphilic molecules (Conn & Drummond, 2013;Rajabalaya et al, 2017) and also tunable release rate (Rizwan & Boyd, 2015;Abd-Allah et al, 2016;Huang & Gui, 2018). LLC exhibits perfect performance on mucosal (Huang et al, 2017), transdermal (Peng et al, 2015;Musa et al, 2017), periodontal (Mei et al, 2017a;Zheng et al, 2018), subcutaneous (Mei et al, 2017b) and other parenteral drug delivery (Wan et al, 2015;Qin et al, 2016), due to its high drug-loading capacity, appropriate viscoelasticity and good biocompatibility (Abd-Allah et al, 2016;Kulkarni & Thareja, 2016).…”

Development and Evaluation of Minocycline Hydrochloride-Loaded In Situ Cubic Liquid Crystal for Intra-Periodontal Pocket Administration

“…Researchers have tried to use liquid crystalline as drug carriers in the treatment of periodontal disease. For example, the precursor system of liquid crystalline phase containing propolis microparticles [ 26 ] and metronidazole [ 27 ] were prepared and characterized. The rheology of systems revealed properties that favored easy injection into the periodontal pocket and subsequent stable retention therein.…”