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    Bone targeting nanoparticle as a new platform of antibiotic agent delivery for the treatment of osteomyelitis

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    Genre
    Thesis/Dissertation
    Date
    2019
    Author
    Guo, Pengbo
    Advisor
    Wong, Ho-Lun
    Committee member
    Blass, Benjamin E.
    Fassihi, Reza
    Buttaro, Bettina A.
    Department
    Pharmaceutical Sciences
    Subject
    Pharmaceutical Sciences
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/614
    
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    DOI
    http://dx.doi.org/10.34944/dspace/596
    Abstract
    Osteomyelitis is a bone infection disease that is caused by microbes. One of the reason that a successful antimicrobial therapy has not been achieved in bone related infection is due to the physiological and structural limitations and multi-drug resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Alendronate, a type of bisphosphonate, is a commonly used drug to treat osteoporosis that can strongly chelate with the calcium ions in bone mineral (hydroxyapatite), could be utilized as an active targeting moiety in a drug delivery system to bone tissues. Since nanomedicine can provide a robust drug delivery platform, with the properties of encapsulating molecules of different hydrophilicity, tunable drug release profile, and potential of differential targeting cells and tissues, we proposed a lipid-polymer nanoparticle system, Bone-Targeting Nanoparticle (BTN), with surface modified with covalently bonded alendronate. In this study, BTN encapsulates linezolid, which has dose-related adverse effect that prevent long duration usage. According to our current results, BTN demonstrates three distinguished traits that potentially improves the therapeutic effect of linezolid towards MRSA induced osteomyelitis: a) a hydrophobic polymeric core that can encapsulate a high amount of linezolid; b) alendronate as a targeting moiety that can guide BTN to bone tissue and accumulate near the site of infection; and c) a PEGylated lipid interface that can enhance the drug release profile and provide increased serum stability relative to standard delivery methods.
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