Injectable in situ Gelling Metronidazole System for Treating Jawbone Infections

dc.contributor.advisorDash, Alekha K.en_US
dc.contributor.authorDash, Shreshthaen_US
dc.contributor.cuauthorDash, Shreshthaen_US
dc.date.accessioned2020-07-07T20:26:52Z
dc.date.available2021-07-11T08:40:21Z
dc.date.issued2020-06-22en_US
dc.degree.committeeSingh, Somnathen_US
dc.degree.committeeChauhan, Harsh V.en_US
dc.degree.disciplinePharmaceutical Science (graduate program)en_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.levelMS (Master of Science)en_US
dc.degree.nameM.S. in Pharmaceutical Sciencesen_US
dc.description.abstractAn untreated dental cavity or an accumulation of bacteria in the side of the teeth or around an implant can cause jawbone infection. This is treated by incision and drainage, root canal treatment or extraction in combination with a prolonged course of antibiotic therapy. Metronidazole is effective against many gram-negative and gram-positive anaerobic bacteria commonly found in dental infections. However, its poor bioavailability in jawbone requires frequent administration of very high dose of metronidazole which leads to serious toxicities. Therefore, there is a need for developing a metronidazole delivery system capable of releasing the drug at the site of jawbone infections at a sustained rate over a period of one week. Hence, this study addresses the development and characterization of an in situ gel forming formulation loaded with metronidazole polymeric nano- and microparticles. We hypothesize that the initial drug release from the delivery system would be provided by the nanoparticles followed by the microparticles, resulting in a sustained drug delivery over a period of one week. An HPLC method for separation and quantification of metronidazole was developed and validated as per USP guidelines. The metronidazole standard curve was linear over a concentration range of 1.6 – 205 µg/ml with R2 > 0.99. Six different in situ gelling delivery system were developed using either poly- DL-lactide (PLA) or chitosan and Pluronic F127/Pluronic F68. In vitro release of metronidazole from PLA-based in situ gelling system was significantly (p < 0.05) less than that from chitosan-Pluronics based systems. The nanoparticles and microparticles were prepared using PLGA. However, chitosan was used for preparing nanoparticles only. These particles containing metronidazole were incorporated in PLA in situ gelling system. These metronidazole particulate systems were further characterized for size, surface charge and morphology. In vitro release of metronidazole from in situ gel was about 90% over a period of one week. The viscosity and yield stress of the in situ gelling formulations were found to be less than 0.4 Pa.s and 2 Pa, respectively suggesting easy syringeability and injectability. The formulations were evaluated for their safety using MTT assay, which indicated 70% cell viability over 72 hours. Future studies should include increasing drug load and evaluation of in vivo efficacy and safety profiles of the delivery system.en_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.embargo.terms2022-01-11
dc.identifier.urihttp://hdl.handle.net/10504/127395
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.rights.holderShreshtha Dashen_US
dc.titleInjectable in situ Gelling Metronidazole System for Treating Jawbone Infectionsen_US
dc.typeDissertation
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