title: Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies.
abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.
authors.affiliation: Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, Taiwan ; Department of Mechanical Engineering, Chang Gung University, Guishan Township, Taiwan.
authors.forename: Yung-Heng
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, Taiwan.
authors.forename: Dave Wei-Chih
authors.initials: DW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, Taiwan.
authors.forename: Chun-Der
authors.initials: CD
authors.lastname: Tai
authors.affiliation: Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, Taiwan ; Department of Mechanical Engineering, Chang Gung University, Guishan Township, Taiwan.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chou
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Guishan Township, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, Taiwan.
authors.forename: Steve Wen-Neng
authors.initials: SW
authors.lastname: Ueng
authors.affiliation: School of Medical Technology, Chang Gung University, Guishan Township, Taiwan.
authors.forename: Err-Cheng
authors.initials: EC
authors.lastname: Chan
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002442:Ceftazidime / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D055664:Electrochemical Techniques; D050296:Microbial Viability / Q000187:drug effects; D057139:Nanofibers / Q000737:chemistry* / Q000633:toxicity; D036103:Nanotechnology; D011817:Rabbits; D013211:Staphylococcus aureus; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014640:Vancomycin; D002442:Ceftazidime
keywords: antibiotics; biodegradable nanofiber-enveloped plates; electrospinning; release characteristics