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

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.