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Each formulation was optimized to achieve desired characteristics in terms of size (ranging from 100 to 400 nm), PDI (less than 0.5), zeta potential (typically negative), and in vitro release profiles for gentamicin. Entrapment percentages varied with gentamicin ranging from 10% to 65%. The chitosan nanoparticles exhibited substantial antimicrobial efficacy, particularly against P. aeruginosa and MRSA, with zones of inhibition ranging from 13 to 24 mm and a complete reduction in colony forming units observed between 3 and 24 h. These chitosan nanoparticle formulations loaded with antimicrobials hold promise for addressing orthopedic complications.<\/jats:p>","DOI":"10.3390\/antibiotics13030208","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T03:30:26Z","timestamp":1708572626000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Evaluation of the Potential of Chitosan Nanoparticles as a Delivery Vehicle for Gentamicin for the Treatment of Osteomyelitis"],"prefix":"10.3390","volume":"13","author":[{"given":"Elliot","family":"Simpson","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Life and Health Sciences, Ulster University, Cromore Rd, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3674-3167","authenticated-orcid":false,"given":"Humera","family":"Sarwar","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Life and Health Sciences, Ulster University, Cromore Rd, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Jack","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Life and Health Sciences, Ulster University, Cromore Rd, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3919-7456","authenticated-orcid":false,"given":"Deborah","family":"Lowry","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Life and Health Sciences, Ulster University, Cromore Rd, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"ref_1","unstructured":"Jlassi, K., Chehimi, M.M., and Thomas, S. (2017). Clay-Polymer Nanocomposites, Elsevier."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"King, M.W., Gupta, B.S., and Guidoin, R. (2013). Biotextiles as Medical Implants, Woodhead Publishing.","DOI":"10.1533\/9780857095602"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Smirnova, N.V., Kolbe, K.A., Dresvyanina, E.N., Grebennikov, S.F., Dobrovolskaya, I.P., Yudin, V.E., Luxbacher, T., and Morganti, P. (2019). Effect of Chitin Nanofibrils on Biocompatibility and Bioactivity of the Chitosan-Based Composite Film Matrix Intended for Tissue Engineering. Materials, 12.","DOI":"10.3390\/ma12111874"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.3390\/md13085156","article-title":"Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications","volume":"13","author":"Cheung","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0168-3659(03)00126-3","article-title":"Chitosan-based gastrointestinal delivery systems","volume":"89","author":"Hejazi","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1586\/eri.11.59","article-title":"Chitosan preparations for wounds and burns: Antimicrobial and wound-healing effects","volume":"9","author":"Dai","year":"2011","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-V\u00e1zquez, M., Vega-Ruiz, B., Ramos-Z\u00fa\u00f1iga, R., Salda\u00f1a-Koppel, D.A., and Qui\u00f1ones-Olvera, L.F. (2015). Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine. Biomed Res. Int., 2015.","DOI":"10.1155\/2015\/821279"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ijfoodmicro.2010.09.012","article-title":"Antimicrobial properties of chitosan and mode of action: A state of the art review","volume":"144","author":"Kong","year":"2010","journal-title":"Int. J. Food Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mohammed, M.A., Syeda, J.T.M., Wasan, K.M., and Wasan, E.K. (2017). An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9040053"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/biom5010003","article-title":"Biodegradable chitosan nanoparticle coatings on titanium for the delivery of BMP-2","volume":"5","author":"Poth","year":"2015","journal-title":"Biomolecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2147\/NSA.S91785","article-title":"Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: Application to the passive encapsulation of [(14)C]-doxorubicin","volume":"8","author":"Masarudin","year":"2015","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1134\/S2079057011010061","article-title":"Bone matrix glycosaminoglycans and osteoporosis development in early aging OXYS rats","volume":"1","author":"Ershov","year":"2011","journal-title":"Adv. Gerontol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sultankulov, B., Berillo, D., Sultankulova, K., Tokay, T., and Saparov, A. (2019). Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine. Biomolecules, 9.","DOI":"10.3390\/biom9090470"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/cid.12599","article-title":"In vivo evaluation of \u03b2-CS\/n-HA with different physical properties as a new bone graft material","volume":"20","author":"Elkholy","year":"2018","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1039\/c4tb00027g","article-title":"Chitosan-based scaffolds for bone tissue engineering","volume":"2","author":"Levengood","year":"2014","journal-title":"J. Mater. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1021\/acs.molpharmaceut.8b00995","article-title":"Nanoparticle-Induced Controlled Drug Delivery Using Chitosan-Based Hydrogel and Scaffold: Application to Bone Regeneration","volume":"16","author":"Mahanta","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.carbpol.2018.05.033","article-title":"Chitosan-based hydrogels: From preparation to biomedical applications","volume":"196","author":"Guilherme","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115734","DOI":"10.1016\/j.carbpol.2019.115734","article-title":"A new waterborne chitosan-based polyurethane hydrogel as a vehicle to transplant bone marrow mesenchymal cells improved wound healing of ulcers in a diabetic rat model","volume":"231","author":"Viezzer","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1021\/acsbiomaterials.2c01297","article-title":"Chitosan Derivatives as Carriers for Drug Delivery and Biomedical Applications","volume":"9","author":"Manna","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115658","DOI":"10.1016\/j.carbpol.2019.115658","article-title":"Applications of chitin and chitosan nanofibers in bone regenerative engineering","volume":"230","author":"Tao","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jamil, B., Habib, H., Abbasi, S.A., Ihsan, A., Nasir, H., and Imran, M. (2016). Development of Cefotaxime Impregnated Chitosan as Nano-antibiotics: De Novo Strategy to Combat Biofilm Forming Multi-drug Resistant Pathogens. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00330"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1208\/s12249-012-9758-7","article-title":"Enhanced antibacterial effect of ceftriaxone sodium-loaded chitosan nanoparticles against intracellular Salmonella typhimurium","volume":"13","author":"Zaki","year":"2012","journal-title":"AAPS PharmSciTech"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hasan, N., Cao, J., Lee, J., Hlaing, S.P., Oshi, M.A., Naeem, M., Ki, M.H., Lee, B.L., Jung, Y., and Yoo, J.W. (2019). Bacteria-Targeted Clindamycin Loaded Polymeric Nanoparticles: Effect of Surface Charge on Nanoparticle Adhesion to MRSA, Antibacterial Activity, and Wound Healing. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050236"},{"key":"ref_24","first-page":"4053","article-title":"Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection","volume":"7","author":"Abdelghany","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10965-019-1854-x","article-title":"Application of multiple regression analysis in optimization of metronidazole-chitosan nanoparticles","volume":"26","author":"Sabbagh","year":"2019","journal-title":"J. Polym. Res."},{"key":"ref_26","first-page":"1352","article-title":"Chitosan nanoparticles as a sustained delivery of penicillin G prepared by ionic gelation technique","volume":"8","author":"Safhi","year":"2014","journal-title":"J. Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"370938","DOI":"10.1155\/2013\/370938","article-title":"Development of oral sustained release rifampicin loaded chitosan nanoparticles by design of experiment","volume":"2013","author":"Patel","year":"2013","journal-title":"J. Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00289-020-03134-2","article-title":"Synthesis and characterization of chitosan nanoparticles containing teicoplanin using sol\u2013gel","volume":"78","author":"Kahdestani","year":"2021","journal-title":"Polym. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abdel-Hakeem, M.A., Abdel Maksoud, A.I., Aladhadh, M.A., Almuryif, K.A., Elsanhoty, R.M., and Elebeedy, D. (2022). Gentamicin&ndash;Ascorbic Acid Encapsulated in Chitosan Nanoparticles Improved In Vitro Antimicrobial Activity and Minimized Cytotoxicity. Antibiotics, 11.","DOI":"10.3390\/antibiotics11111530"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.2147\/IJN.S406649","article-title":"Gentiopicroside-Loaded Chitosan Nanoparticles Inhibit TNF-\u03b1-Induced Proliferation and Inflammatory Response in HaCaT Keratinocytes and Ameliorate Imiquimod-Induced Dermatitis Lesions in Mice","volume":"18","author":"Zhao","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1177\/0885328214535452","article-title":"Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based antibiotic therapy in the treatment of chronic osteomyelitis","volume":"29","author":"Beenken","year":"2014","journal-title":"J. Biomater. Appl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3390\/membranes13060542","article-title":"Chitosan-Based Membranes as Gentamicin Carriers for Biomedical Applications&mdash;Influence of Chitosan Molecular Weight","volume":"13","author":"Supernak","year":"2023","journal-title":"Membranes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2147\/IJN.S127715","article-title":"Efficient induction of antimicrobial activity with vancomycin nanoparticle-loaded poly (trimethylene carbonate) localized drug delivery system","volume":"12","author":"Zhang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_34","first-page":"17","article-title":"Increased osteoblast viability at alkaline pH in vitro provides a new perspective on bone regeneration","volume":"10","author":"Galow","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1080\/02652040802365182","article-title":"Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion","volume":"26","author":"Lu","year":"2009","journal-title":"J. Microencapsul."},{"key":"ref_36","first-page":"1","article-title":"Formulation and Evaluation of Metronidazole Loaded Chitosan Nanoparticles","volume":"4","author":"Ruchika","year":"2016","journal-title":"Int. J. Sci. Res. Methodol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"898910","DOI":"10.1155\/2010\/898910","article-title":"Preparation and Characterization of Water-Soluble Chitosan Nanoparticles as Protein Delivery System","volume":"2010","author":"Zhang","year":"2010","journal-title":"J. Nanomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.1021\/bm3014236","article-title":"Salt-assisted mechanistic analysis of chitosan\/tripolyphosphate micro- and nanogel formation","volume":"13","author":"Huang","year":"2012","journal-title":"Biomacromolecules"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"427","DOI":"10.15171\/apb.2017.051","article-title":"Nanoparticles of Chitosan Loaded Ciprofloxacin: Fabrication and Antimicrobial Activity","volume":"7","author":"Sobhani","year":"2017","journal-title":"Adv. Pharm. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1038\/s41598-018-23064-4","article-title":"Parameters influencing the size of chitosan-TPP nano- and microparticles","volume":"8","author":"Sreekumar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","first-page":"1851","article-title":"Chitosan-Pluronic nanoparticles as oral delivery of anticancer gemcitabine: Preparation and in vitro study","volume":"7","author":"Hosseinzadeh","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"de Carvalho, F.G., Magalh\u00e3es, T.C., Teixeira, N.M., Gondim, B.L.C., Carlo, H.L., Dos Santos, R.L., de Oliveira, A.R., and Denadai, \u00c2.M.L. (2019). Synthesis and characterization of TPP\/chitosan nanoparticles: Colloidal mechanism of reaction and antifungal effect on C. albicans biofilm formation. Mater. Sci. Eng. C Mater. Biol. Appl., 104.","DOI":"10.1016\/j.msec.2019.109885"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4028\/www.scientific.net\/KEM.819.27","article-title":"Electrostatic Effects of Metronidazole Loaded in Chitosan-Pectin Polyelectrolyte Complexes","volume":"819","author":"Limsitthichaikoon","year":"2019","journal-title":"Key Eng. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"125","DOI":"10.22159\/ajpcr.2017.v10i6.17643","article-title":"Comparative mucopenetration ability of metronidazole loaded chitosan and pegylated chitosan nanoparticles","volume":"10","author":"Sukhbir","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.carbpol.2011.03.051","article-title":"Preparation, characterization and in vitro release of chitosan nanoparticles loaded with gentamicin and salicylic acid","volume":"85","author":"Ji","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.3797\/scipharm.1208-02","article-title":"Transfersomes: A novel vesicular carrier for enhanced transdermal delivery of sertraline: Development, characterization, and performance evaluation","volume":"80","author":"Gupta","year":"2012","journal-title":"Sci. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0732-8893(98)00139-4","article-title":"Susceptibility testing of Clostridium difficile against metronidazole and vancomycin by disk diffusion and Etest","volume":"34","author":"Wong","year":"1999","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1296","DOI":"10.31661\/gmj.v8i0.1296","article-title":"Gentamicin-Loaded Chitosan Nanoparticles Improve Its Therapeutic Effects on Brucella-Infected J774A.1 Murine Cells","volume":"8","author":"Razei","year":"2019","journal-title":"Galen Med. J."},{"key":"ref_49","first-page":"239","article-title":"Sensitivity of ESBL-Producing Gram-Negative Bacteria to Essential Oils, Plant Extracts, and Their Isolated Compounds","volume":"1","author":"Bencsik","year":"2016","journal-title":"Antibiot. Resist."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/jac\/47.6.789","article-title":"Antimicrobial susceptibility of Pseudomonas aeruginosa: Results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test","volume":"47","author":"Henwood","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Naimi, H.M., Rasekh, H., Noori, A.Z., and Bahaduri, M.A. (2017). Determination of antimicrobial susceptibility patterns in Staphylococcus aureus strains recovered from patients at two main health facilities in Kabul, Afghanistan. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2844-4"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ijantimicag.2005.10.021","article-title":"Antibacterial activity of liposomal gentamicin against Pseudomonas aeruginosa: A time-kill study","volume":"27","author":"Rukholm","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.2147\/IJN.S247088","article-title":"Injectable Chitosan-Based Thermosensitive Hydrogel\/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis","volume":"15","author":"Tao","year":"2020","journal-title":"Int. J. 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