title: The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers.
abstract: Infections of the musculoskeletal system present a serious problem with regard to the field of orthopedic and trauma medicine. The aim of the experiment described in this study was to develop a resorbable nanostructured composite layer with the controlled elution of antibiotics. The layer is composed of collagen, hydroxyapatite nanoparticles, and vancomycin hydrochloride (10 wt%). The stability of the collagen was enhanced by means of cross-linking. Four cross-linking agents were studied, namely an ethanol solution, a phosphate buffer solution of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, genipin, and nordihydroguaiaretic acid. High performance liquid chromatography was used so as to characterize the in vitro release rates of the vancomycin and its crystalline degradation antibiotically inactive products over a 21-day period. The maximum concentration of the released active form of vancomycin (approximately 265 mg/L) exceeded the minimum inhibitory concentration up to an order of 17 times without triggering the burst releasing effect. At the end of the experiment, the minimum inhibitory concentration was exceeded by up to 6 times (approximately 100 mg/L). It was determined that the modification of collagen with hydroxyapatite nanoparticles does not negatively influence the sustainable release of vancomycin. The balance of vancomycin and its degradation products was observed after 14 days of incubation.
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic; Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague 6, Czech Republic. Electronic address: suchyt@irsm.cas.cz.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Suchý
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Šupová
authors.affiliation: Department of Medical Chemistry and Clinical Biochemistry, Charles University, 2nd Medical School and University Hospital Motol, Prague 5, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Klapková
authors.affiliation: Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague 6, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Horný
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Rýglová
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: Margit
authors.initials: M
authors.lastname: Žaloudková
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: Zbyněk
authors.initials: Z
authors.lastname: Sucharda
authors.affiliation: 1st Department of Orthopaedics, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Ballay
authors.affiliation: Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Veselý
authors.affiliation: Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague 6, Czech Republic.
authors.forename: Hynek
authors.initials: H
authors.lastname: Chlup
authors.affiliation: Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Denk
mesh_terms: D002234:Carbodiimides / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite; D008744:Methylamines / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D014640:Vancomycin / Q000737:chemistry*
chemical_list: C569779:1-(3-dimethylaminopropyl)-dimethylaminopropyl-ethylcarbodiimide hydrochloride; D002234:Carbodiimides; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008744:Methylamines; D014640:Vancomycin; D003094:Collagen; D017886:Durapatite
keywords: HPLC; anti-infectives; coating; controlled release; degradation products; drug delivery systems; nanoparticles; pharmacokinetics; polymeric drug delivery systems