|
|
Drug-release kinetics characterization of gentamicin from TiO2 nanotubes and its antibacterial activity in vitro |
FENG Mingguang1,LIU Zhongtang2, WANG Liqiang3, XU Li1, YANG Haitao1, WANG Jian1, WANG Haiyang1,and QING Shixin1 |
1.Department of Orthopedics, Shanghai Municipal Corps Hospital Chinese People’s Armed Police Force, Shanghai 201103, China; 2.Department of Orthopedics, the Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai 200233,China; 3.College of Materials Science and Engineering, Shanghai Jiaotong University, Shanghai 200240, China |
|
|
Abstract Objective To determine the release kinetics of gentamicin from the TiO2 nanotubes(TNS-G), and to detect its antibacterial activity in vitro. Methods TiO2 nanotubes (NTS) were fabricated on the titanium surface by electrochemical anodization. These nanotubes were loaded with gentamicin using a lyophilization method and vacuum drying, and its pharmacokinetics was detected in phosphate buffer. Staphylococcus aureus was used to study the antibacterial properties of the NTS-G. There were three study groups: the commercially pure titanium(Cp-Ti)group, the NTS group, and the NTS-G group.We compared the antibacterial efficacy with each other by bacterial adhesion and colony counting in bacterial culture. Results Drug release of NTS-G could be divided into two parts: initial burst release and relatively slow release.The fast initial concentration was 51.50 μg/ml , and 73.13 μg/ml at the 6 th hours. Most of load gentamicin was released within approximately 9 hours.In the second phase, different drug release kinetics were observed, with very slow and linearly increasing cumulative release over a period of 90 h. The drug concentration was maintained at about 89.10 μg/ml. We found that NTS-G could significantly inhibit bacterial adhesion and bioflm formation, compared with Cp-Ti or NTS, (P<0.05). Conclusions Titanium dioxide nanotubes loaded with antibiotics can deliver a high concentration of antibiotics locally at a specifc site, thereby providing a new strategy to prevent implant-associated infections.
|
Received: 22 April 2015
|
|
|
|
|
[11] |
Gulati K, Aw M S, Findlay D, et al. Local drug delivery to the bone bydrug-releasing implants: perspectives of nano-engineered titania nanotube arrays[J].TherDeliv,2012,3(7):857-873.
|
[1] |
Zhang Hangzhou, Yu Sun, Ang Tian, et al. Improved antibacterial activity and biocompatibility on vancomycin-loaded TiO2 nanotubes: in vivo and in vitro studies[J].International Journal of Nanomedicine, 2013(8):4379-4389.
|
[12] |
Berger R A, Jacobs J J, Quigley L R, et al. Primary cementlessacetabular reconstruction in patients younger than 50 years old. 7- to 11-year results[J]. ClinOrthopRelat Res, 1997,(344):216-226.
|
[2] |
Bozic K J, Lau E, Chiu V, et al. The epidemiology of revision total knee arthroplasty in the United States[J]. ClinOrthopRelat Res,2010,468(1):45-51.
|
[13] |
Porter J R, Ruckh T T, Popat K C. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies[J].BiotechnolProg, 2009, 25(6):1539-1560.
|
[3] |
Puckett S D, Taylor E, Raimondo T, et al. The relationship between the nanostructure of titanium surfaces and bacterial attachment[J]. Biomaterials,2010,31(4):706-713.
|
[14] |
Wu P, Grainger D W. Drug/device combinations for local drug therapies and infection prophylaxis[J].Biomaterials,2006,27(11):2450-2467.
|
[4] |
Hetrick E M, Schoenfsch M H. Reducing implant-related infections: active release strategies[J]. ChemSoc Rev,2006,35(9):780-789.
|
[15] |
Liu H, Webster T J. Nanomedicine for implants: a review of studies and necessary experimental tools[J]. Biomaterials,2007,28(2):354-369.
|
[5] |
Kurtz S M, Lau E, Schmier J, et al. Infection burden for hip and knee arthroplasty in the United States[J]. J Arthroplasty,2008,23(7):984-991.
|
[16] |
Ghicov A, Schmuki P. Self-ordering electrochemistry: a review on growth and functionality of TiO2 nanotubes and other self-aligned MO(x) structures[J].ChemCommun(Camb),2009,(20):2791-2808.
|
[6] |
Ribeiro M, Monteiro F J, Ferraz M P. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions[J]. Biomatter,2012,2(4):176-194.
|
[17] |
Losic D, Simovic S. Self-ordered nanopore and nanotube platforms for drug delivery applications[J]. Expert Opin Drug Deliv,2009,6(12): 1363-1381.
|
[7] |
Costerton J W, Stewart P S, Greenberg E P. Bacterial bioflms: a common cause of persistent infections[J].Science, 1999,284(5418):1318-1322.
|
[18] |
Gulati K, Aw M S, Losic D. Drug-eluting Ti wires with titania nanotube arrays for bone fxation and reduced bone infection[J]. Nanoscale Res Lett,2011,(6):571.
|
[8] |
Davies D. Understanding bioflm resistance to antibacterial agents[J]. Nat Rev Drug Discov, 2003,2(2):114-122.
|
[9] |
Popat K C, Eltgroth M, LaTempa T J, et al. Titania nanotubes: a novel platform for drug-eluting coatings for medical implants[J].Small,2007,3(11):1878-1881.
|
[19] |
Popat K C, Eltgroth M, Latempa T J, et al. Decreased Staphylococcus Epidermis adhesion and increased osteoblast functional-ity on antibiotic-loaded titania nanotubes[J]. Biomaterials,2007,28(32): 4880-4888.
|
[10] |
Diefenbeck M, Mückley T, Hofmann G O. Prophylaxis and treatment of implant-related infections by local application of antibiotics[J]. Injury,2006,37(2):95-104.
|
[20] |
Wen taolin,hong lueTan,Zhaoling Duan,et al: Inhibited bacterial bioflm formation and improved osteogenic activity on gentamicin-loaded titania nanotubes with various diameters[J]. International Journal of Nanomedicine,2014,(9):1215-1230.
|
[21] |
Neoh K G, Hu X, Zheng D, et al. Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces[J].Biomaterials, 2012,33(10):2813-2822.
|
[11] |
Gulati K, Aw M S, Findlay D, et al. Local drug delivery to the bone bydrug-releasing implants: perspectives of nano-engineered titania nanotube arrays[J].TherDeliv,2012,3(7):857-873.
|
[12] |
Berger R A, Jacobs J J, Quigley L R, et al. Primary cementlessacetabular reconstruction in patients younger than 50 years old. 7- to 11-year results[J]. ClinOrthopRelat Res, 1997,(344):216-226.
|
[22] |
Ercan B, Taylor E, Alpaslan E, et al. Diameter of titanium nanotubes influences anti-bacterial efficacy[J]. Nanotechnology,2011,22(29):292-295.
|
[23] |
Arciola C R, Campoccia D, Speziale P, et al. Bioflm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for bioflm-resistant materials[J]. Biomaterials,2012,33(26):5967-5982.
|
[13] |
Porter J R, Ruckh T T, Popat K C. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies[J].BiotechnolProg, 2009, 25(6):1539-1560.
|
[24] |
Soundrapandian C, Sa B, Datta S. Organic-inorganic composites for bone drug delivery[J]. AAPS Pharm Sci Tech, 2009,10(4):1158-1171.
|
[14] |
Wu P, Grainger D W. Drug/device combinations for local drug therapies and infection prophylaxis[J].Biomaterials,2006,27(11):2450-2467.
|
[25] |
Simchi A, Tamjid E, Pishbin F, et al. Recent progress in inorganic and composite coatings with bactericidal capability for orthopaedic applications[J].Nanomedicine,2011,7(1):22-39.
|
[15] |
Liu H, Webster T J. Nanomedicine for implants: a review of studies and necessary experimental tools[J]. Biomaterials,2007,28(2):354-369.
|
[16] |
Ghicov A, Schmuki P. Self-ordering electrochemistry: a review on growth and functionality of TiO2 nanotubes and other self-aligned MO(x) structures[J].ChemCommun(Camb),2009,(20):2791-2808.
|
[26] |
Bjursten L M, Rasmusson L, Oh S, et al. Titanium dioxide nanotubes enhance bone bonding in vivo[J]. J Biomed Mater Res A,2010,92(3):1218-1224.
|
[27] |
Arciola C R, Campoccia D, Gamberini S, et al. Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis clinical isolates from orthopaedic implant infections[J]. Biomaterials, 2005,26(33):6530-6535.
|
[17] |
Losic D, Simovic S. Self-ordered nanopore and nanotube platforms for drug delivery applications[J]. Expert Opin Drug Deliv,2009,6(12): 1363-1381.
|
[28] |
Rathbone C R, Cross J D, Brown K V, et al. Effect of various concentrations of antibiotics on osteogenic cell viability and activity[J]. J Orthop Res, 2011,29(7):1070-1074.
|
[18] |
Gulati K, Aw M S, Losic D. Drug-eluting Ti wires with titania nanotube arrays for bone fxation and reduced bone infection[J]. Nanoscale Res Lett,2011,(6):571.
|
[19] |
Popat K C, Eltgroth M, Latempa T J, et al. Decreased Staphylococcus Epidermis adhesion and increased osteoblast functional-ity on antibiotic-loaded titania nanotubes[J]. Biomaterials,2007,28(32): 4880-4888.
|
[20] |
Wen taolin,hong lueTan,Zhaoling Duan,et al: Inhibited bacterial bioflm formation and improved osteogenic activity on gentamicin-loaded titania nanotubes with various diameters[J]. International Journal of Nanomedicine,2014,(9):1215-1230.
|
[21] |
Neoh K G, Hu X, Zheng D, et al. Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces[J].Biomaterials, 2012,33(10):2813-2822.
|
[22] |
Ercan B, Taylor E, Alpaslan E, et al. Diameter of titanium nanotubes influences anti-bacterial efficacy[J]. Nanotechnology,2011,22(29):292-295.
|
[23] |
Arciola C R, Campoccia D, Speziale P, et al. Bioflm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for bioflm-resistant materials[J]. Biomaterials,2012,33(26):5967-5982.
|
[24] |
Soundrapandian C, Sa B, Datta S. Organic-inorganic composites for bone drug delivery[J]. AAPS Pharm Sci Tech, 2009,10(4):1158-1171.
|
[25] |
Simchi A, Tamjid E, Pishbin F, et al. Recent progress in inorganic and composite coatings with bactericidal capability for orthopaedic applications[J].Nanomedicine,2011,7(1):22-39.
|
[26] |
Bjursten L M, Rasmusson L, Oh S, et al. Titanium dioxide nanotubes enhance bone bonding in vivo[J]. J Biomed Mater Res A,2010,92(3):1218-1224.
|
[27] |
Arciola C R, Campoccia D, Gamberini S, et al. Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis clinical isolates from orthopaedic implant infections[J]. Biomaterials, 2005,26(33):6530-6535.
|
[28] |
Rathbone C R, Cross J D, Brown K V, et al. Effect of various concentrations of antibiotics on osteogenic cell viability and activity[J]. J Orthop Res, 2011,29(7):1070-1074.
|
[1] |
. [J]. , 2012, 23(11): 1006-1006. |
|
|
|
|