title: Characterization of crosslinked high amylose starch matrix implants. 2. In vivo release of ciprofloxacin.
abstract: The purpose of this study was to develop a crosslinked high amylose starch (CLHAS) matrix implant as a sustained antimicrobial delivery system for local prevention and/or treatment of osteomyelitis. Implants (200 mg) of CLHAS containing 2.5% (5 mg), 7.5% (15 mg), 15.0% (30 mg) and 20.0% (40 mg) of ciprofloxacin (CFX), were prepared by direct compression of dry blends. Rabbits were administered six 2.5, two 7.5, one 15.0 or one 20.0%-CFX implants along the femur between the quadriceps and biceps femoris muscles to determine systemic (serum) versus local (muscle and bone) CFX concentrations over 1 month. Blood samples were taken throughout the study for CFX assay. Muscle and femur were collected at 3, 7, 14, 21 and 28 days after implantation for host response evaluation and CFX assay. Residual polymer was explanted to determine the remaining dose of CFX. All animals remained healthy during the study. Local tissue reaction was mild and limited to the implantation site. Serum CFX concentrations remained low regardless of implant loading. Increased drug loading resulted in a higher and longer release of CFX in muscle and in bone. Local CFX concentrations were detected largely in excess of the MIC over 28 days with 20.0%-CFX implants. More residual CFX in polymer was detected over a longer period of time at high loading. These results strongly support the development of CLHAS implants for local antibacterial therapy.
authors.affiliation: Faculty of Pharmacy, University of Montreal, C.P. 6128, Succ. Centre-ville, Montreal (QC), H3C 3J7, Canada. cyril.desevaux@umontreal.ca
authors.forename: Cyril
authors.initials: C
authors.lastname: Désévaux
authors.forename: Vincent
authors.initials: V
authors.lastname: Lenaerts
authors.forename: Christiane
authors.initials: C
authors.lastname: Girard
authors.forename: Pascal
authors.initials: P
authors.lastname: Dubreuil
mesh_terms: D020341:Absorbable Implants; D000688:Amylose / Q000737:chemistry*; D000818:Animals; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004339:Drug Compounding; D004343:Drug Implants; D005269:Femur / Q000737:chemistry*; D009132:Muscles / Q000737:chemistry*; D011817:Rabbits; D013213:Starch / Q000737:chemistry*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D003432:Cross-Linking Reagents; D004343:Drug Implants; D002939:Ciprofloxacin; D013213:Starch; D000688:Amylose