title: Prolonged local antibiotics delivery from hydroxyapatite functionalised with cyclodextrin polymers.
abstract: Per-operative infection is a common complication for bone-graft surgery. Combining antiseptic agents with graft materials may offer a solution by increasing local drug concentration at target sites. Aiming to achieve a sustained local antibiotic (ATB) delivery for a widely applied bone substitute material - hydroxyapatite (HA), we attempted incorporating hydroxypropyl-beta-cyclodextrin polymer (polyHPbetaCD) into microporous HA via impregnating either in a CD monomers mixture solution or a pre-synthesized CD polymer solution, followed by thermal fixation processing. In such functionalised material (CD-HA), polyHPbetaCD could entrap ATBs and release them progressively. Infrared-spectroscopic analysis confirmed the presence of polyHPbetaCD in functionalised HA via both processing pathways; polyHPbetaCD functionalisation yields were quantitated by thermogravimetric analysis for optimising the processing regime. Ciprofloxacin (CFX) and vancomycin (VCM), commonly applied in orthopaedics, have been respectively loaded on CD-HA by dip-coating. For both ATBs, kinetic release test in phosphate buffered saline showed significantly increased initial-burst amount and prolonged release from CD-HA compared with those from non-functionalised HA. Encouragingly, ATBs loaded CD-HA also revealed a prolonged bacteriostatic activity against Staphylococcus aureus and progressively increased cytocompatibility to osteoblasts (MC3T3-E1). Overall, polyHPbetaCD functionalisation on HA could be an effective drug-delivery model for loading different drug molecules in prevention of infection.
authors.affiliation: Laboratoire de Chimie Organique et Macromoléculaire UMR CNRS8009, Université Lille Nord de France, 59655 Villeneuve d'Ascq, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leprêtre
authors.forename: Feng
authors.initials: F
authors.lastname: Chai
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Hornez
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vermet
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
authors.forename: Michel
authors.initials: M
authors.lastname: Descamps
authors.forename: Hartmut F
authors.initials: HF
authors.lastname: Hildebrand
authors.forename: Bernard
authors.initials: B
authors.lastname: Martel
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D016025:Bone Transplantation; D002939:Ciprofloxacin / Q000008:administration & dosage; D003505:Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D051379:Mice; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000378:metabolism; D014640:Vancomycin / Q000008:administration & dosage
chemical_list: D000890:Anti-Infective Agents; D003505:Cyclodextrins; D011108:Polymers; D002939:Ciprofloxacin; D014640:Vancomycin; D017886:Durapatite