The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers

• Published in: Journal of pharmaceutical sciences Vol. 105; no. 3; p. 1288
• Main Authors: Suchý, Tomáš, Šupová, Monika, Klapková, Eva, Horný, Lukáš, Rýglová, Šárka, Žaloudková, Margit, Braun, Martin, Sucharda, Zbyněk, Ballay, Rastislav, Veselý, Jan, Chlup, Hynek, Denk, František
• Format: Journal Article
• Language: English
• Published: United States 01-03-2016
• Subjects: Carbodiimides - chemistry; Collagen - chemistry; Delayed-Action Preparations - chemistry; Drug Carriers - chemistry; Drug Delivery Systems - methods; Durapatite; Methylamines - chemistry; Nanoparticles - chemistry; Nanostructures - chemistry; Vancomycin - chemistry; drug delivery systems; controlled release; coating; nanoparticles; degradation products; pharmacokinetics; anti-infectives; polymeric drug delivery systems; HPLC
• ISSN: 1520-6017
• DOI: 10.1016/S0022-3549(15)00175-6

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.