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Published in: BMC Musculoskeletal Disorders 1/2006

Open Access 01-12-2006 | Research article

In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

Authors: Hein P Stallmann, Chris Faber, Antonius LJJ Bronckers, Arie V Nieuw Amerongen, Paul IJM Wuisman

Published in: BMC Musculoskeletal Disorders | Issue 1/2006

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Abstract

Background

Polymethyl-methacrylate (PMMA) beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade.

Methods

As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days), the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus.

Results

All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days). The relative release of all cements (36–85%) and granules (30–62%) was higher than previously reported for injectable PMMA-cements (up to 17%) and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface.

Conclusion

The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained) may be achieved.
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Literature
1.
go back to reference Cierny GIII, Mader JT, Penninck JJ: A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003, 7-24. 10.1097/01.blo.0000088564.81746.62. Cierny GIII, Mader JT, Penninck JJ: A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003, 7-24. 10.1097/01.blo.0000088564.81746.62.
2.
go back to reference Le Saux N, Howard A, Barrowman NJ, Gaboury I, Sampson M, Moher D: Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review. BMC Infect Dis. 2002, 2: 16-10.1186/1471-2334-2-16.CrossRefPubMedPubMedCentral Le Saux N, Howard A, Barrowman NJ, Gaboury I, Sampson M, Moher D: Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review. BMC Infect Dis. 2002, 2: 16-10.1186/1471-2334-2-16.CrossRefPubMedPubMedCentral
3.
go back to reference Henry SL, Galloway KP: Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations. Clin Pharmacokinet. 1995, 29: 36-45.CrossRefPubMed Henry SL, Galloway KP: Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations. Clin Pharmacokinet. 1995, 29: 36-45.CrossRefPubMed
4.
go back to reference Neut D, van de Belt H, Stokroos I, van Horn JR, van der Mei HC, Busscher HJ: Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother. 2001, 47: 885-891. 10.1093/jac/47.6.885.CrossRefPubMed Neut D, van de Belt H, Stokroos I, van Horn JR, van der Mei HC, Busscher HJ: Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother. 2001, 47: 885-891. 10.1093/jac/47.6.885.CrossRefPubMed
5.
go back to reference Walenkamp GH: Gentamicin PMMA beads and other local antibiotic carriers in two-stage revision of total knee infection: a review. J Control Release. 2001, 13 Spec No 1: 66-72. Walenkamp GH: Gentamicin PMMA beads and other local antibiotic carriers in two-stage revision of total knee infection: a review. J Control Release. 2001, 13 Spec No 1: 66-72.
6.
go back to reference Wichelhaus TA, Dingeldein E, Rauschmann M, Kluge S, Dieterich R, Schafer V, Brade V: Elution characteristics of vancomycin, teicoplanin, gentamicin and clindamycin from calcium sulphate beads. J Antimicrob Chemother. 2001, 48: 117-119. 10.1093/jac/48.1.117.CrossRefPubMed Wichelhaus TA, Dingeldein E, Rauschmann M, Kluge S, Dieterich R, Schafer V, Brade V: Elution characteristics of vancomycin, teicoplanin, gentamicin and clindamycin from calcium sulphate beads. J Antimicrob Chemother. 2001, 48: 117-119. 10.1093/jac/48.1.117.CrossRefPubMed
7.
go back to reference Humphrey JS, Mehta S, Seaber AV, Vail TP: Pharmacokinetics of a degradable drug delivery system in bone. Clin Orthop Relat Res. 1998, 218-224. 10.1097/00003086-199804000-00027. Humphrey JS, Mehta S, Seaber AV, Vail TP: Pharmacokinetics of a degradable drug delivery system in bone. Clin Orthop Relat Res. 1998, 218-224. 10.1097/00003086-199804000-00027.
8.
go back to reference Nijhof MW, Stallmann HP, Vogely HC, Fleer A, Schouls LM, Dhert WJ, Verbout AJ: Prevention of infection with tobramycin-containing bone cement or systemic cefazolin in an animal model. J Biomed Mater Res. 2000, 52: 709-715. 10.1002/1097-4636(20001215)52:4<709::AID-JBM16>3.0.CO;2-W.CrossRefPubMed Nijhof MW, Stallmann HP, Vogely HC, Fleer A, Schouls LM, Dhert WJ, Verbout AJ: Prevention of infection with tobramycin-containing bone cement or systemic cefazolin in an animal model. J Biomed Mater Res. 2000, 52: 709-715. 10.1002/1097-4636(20001215)52:4<709::AID-JBM16>3.0.CO;2-W.CrossRefPubMed
9.
go back to reference Blokhuis TJ, Termaat MF, den Boer FC, Patka P, Bakker FC, Haarman HJ: Properties of calcium phosphate ceramics in relation to their in vivo behavior. J Trauma. 2000, 48: 179-186.CrossRefPubMed Blokhuis TJ, Termaat MF, den Boer FC, Patka P, Bakker FC, Haarman HJ: Properties of calcium phosphate ceramics in relation to their in vivo behavior. J Trauma. 2000, 48: 179-186.CrossRefPubMed
10.
go back to reference Faber C, Stallmann HP, Lyaruu DM, de Blieck JM, Bervoets TJ, Nieuw Amerongen AV, Wuisman PI: Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads. J Antimicrob Chemother. 2003, 51: 1359-1364. 10.1093/jac/dkg258.CrossRefPubMed Faber C, Stallmann HP, Lyaruu DM, de Blieck JM, Bervoets TJ, Nieuw Amerongen AV, Wuisman PI: Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads. J Antimicrob Chemother. 2003, 51: 1359-1364. 10.1093/jac/dkg258.CrossRefPubMed
11.
go back to reference Stallmann HP, Faber C, Slotema ET, Lyaruu DM, Bronckers AL, Nieuw Amerongen AV, Wuisman PI: Continuous-release or burst-release of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11) from calcium phosphate bone substitutes. J Antimicrob Chemother. 2003, 52: 853-855. 10.1093/jac/dkg443.CrossRefPubMed Stallmann HP, Faber C, Slotema ET, Lyaruu DM, Bronckers AL, Nieuw Amerongen AV, Wuisman PI: Continuous-release or burst-release of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11) from calcium phosphate bone substitutes. J Antimicrob Chemother. 2003, 52: 853-855. 10.1093/jac/dkg443.CrossRefPubMed
12.
go back to reference van de Belt H, Neut D, van Horn JR, van der Mei HC, Schenk W, Busscher HJ: Antibiotic Resistance - to treat or not to treat?. Nat Med. 1999, 5: 358-359. 10.1038/7330.CrossRefPubMed van de Belt H, Neut D, van Horn JR, van der Mei HC, Schenk W, Busscher HJ: Antibiotic Resistance - to treat or not to treat?. Nat Med. 1999, 5: 358-359. 10.1038/7330.CrossRefPubMed
13.
go back to reference Bohner M, Lemaitre J, Van Landuyt P, Zambelli PY, Merkle HP, Gander B: Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system. J Pharm Sci. 1997, 86: 565-572. 10.1021/js960405a.CrossRefPubMed Bohner M, Lemaitre J, Van Landuyt P, Zambelli PY, Merkle HP, Gander B: Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system. J Pharm Sci. 1997, 86: 565-572. 10.1021/js960405a.CrossRefPubMed
14.
go back to reference van de Belt H, Neut D, Uges DR, Schenk W, van Horn JR, van der Mei HC, Busscher HJ: Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials. 2000, 21: 1981-1987. 10.1016/S0142-9612(00)00082-X.CrossRefPubMed van de Belt H, Neut D, Uges DR, Schenk W, van Horn JR, van der Mei HC, Busscher HJ: Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials. 2000, 21: 1981-1987. 10.1016/S0142-9612(00)00082-X.CrossRefPubMed
15.
go back to reference Kühn KD: Bone cements : up-to-date comparison of physical and chemical properties of commercial materials. 2000, Springer, London, UKCrossRef Kühn KD: Bone cements : up-to-date comparison of physical and chemical properties of commercial materials. 2000, Springer, London, UKCrossRef
16.
go back to reference van de Belt H, Neut D, Schenk W, van Horn JR, van der Mei HC, Busscher HJ: Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand. 2000, 71: 625-629. 10.1080/000164700317362280.CrossRefPubMed van de Belt H, Neut D, Schenk W, van Horn JR, van der Mei HC, Busscher HJ: Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand. 2000, 71: 625-629. 10.1080/000164700317362280.CrossRefPubMed
17.
go back to reference Faber C, Hoogendoorn RJ, Lyaruu DM, Stallmann HP, van Marle J, Nieuw Amerongen AV, Smit TH, Wuisman PI: The effect of the antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement. Biomaterials. 2005, 26: 5717-5726. 10.1016/j.biomaterials.2005.01.036.CrossRefPubMed Faber C, Hoogendoorn RJ, Lyaruu DM, Stallmann HP, van Marle J, Nieuw Amerongen AV, Smit TH, Wuisman PI: The effect of the antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement. Biomaterials. 2005, 26: 5717-5726. 10.1016/j.biomaterials.2005.01.036.CrossRefPubMed
18.
19.
go back to reference Ipsen T, Jorgensen PS, Damholt V, Torholm C: Gentamicin-collagen sponge for local applications. 10 cases of chronic osteomyelitis followed for 1 year. Acta Orthop Scand. 1991, 62: 592-594.CrossRefPubMed Ipsen T, Jorgensen PS, Damholt V, Torholm C: Gentamicin-collagen sponge for local applications. 10 cases of chronic osteomyelitis followed for 1 year. Acta Orthop Scand. 1991, 62: 592-594.CrossRefPubMed
20.
go back to reference Soriano I, Evora C: Formulation of calcium phosphates/poly (d,l-lactide) blends containing gentamicin for bone implantation. J Control Release. 2000, 68: 121-134. 10.1016/S0168-3659(00)00251-0.CrossRefPubMed Soriano I, Evora C: Formulation of calcium phosphates/poly (d,l-lactide) blends containing gentamicin for bone implantation. J Control Release. 2000, 68: 121-134. 10.1016/S0168-3659(00)00251-0.CrossRefPubMed
21.
go back to reference Higuchi T: Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963, 52: 1145-1149.CrossRefPubMed Higuchi T: Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963, 52: 1145-1149.CrossRefPubMed
22.
go back to reference Hendriks JG, Neut D, van Horn JR, van der Mei HC, Busscher HJ: The release of gentamicin from acrylic bone cements in a simulated prosthesis-related interfacial gap. J Biomed Mater Res. 2003, 64B: 1-5. 10.1002/jbm.b.10391.CrossRef Hendriks JG, Neut D, van Horn JR, van der Mei HC, Busscher HJ: The release of gentamicin from acrylic bone cements in a simulated prosthesis-related interfacial gap. J Biomed Mater Res. 2003, 64B: 1-5. 10.1002/jbm.b.10391.CrossRef
23.
go back to reference McLaren AC, McLaren SG, Nelson CL, Wassell DL, Olsen KM: The effect of sampling method on the elution of tobramycin from calcium sulfate. Clin Orthop. 2002, 54-57. McLaren AC, McLaren SG, Nelson CL, Wassell DL, Olsen KM: The effect of sampling method on the elution of tobramycin from calcium sulfate. Clin Orthop. 2002, 54-57.
24.
go back to reference Perry AC, Rouse MS, Khaliq Y, Piper KE, Hanssen AD, Osmon DR, Steckelberg JM, Patel R: Antimicrobial release kinetics from polymethylmethacrylate in a novel continuous flow chamber. Clin Orthop. 2002, 49-53. Perry AC, Rouse MS, Khaliq Y, Piper KE, Hanssen AD, Osmon DR, Steckelberg JM, Patel R: Antimicrobial release kinetics from polymethylmethacrylate in a novel continuous flow chamber. Clin Orthop. 2002, 49-53.
25.
go back to reference Zuluaga AF, Galvis W, Jaimes F, Vesga O: Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study. BMC Infect Dis. 2002, 2: 8-10.1186/1471-2334-2-8.CrossRefPubMedPubMedCentral Zuluaga AF, Galvis W, Jaimes F, Vesga O: Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study. BMC Infect Dis. 2002, 2: 8-10.1186/1471-2334-2-8.CrossRefPubMedPubMedCentral
26.
go back to reference Stallmann HP, Faber C, Bronckers AL, Nieuw Amerongen AV, Wuisman PI: Osteomyelitis prevention in rabbits using antimicrobial peptide hLF1-11- or gentamicin-containing calcium phosphate cement. J Antimicrob Chemother. 2004, 54: 472-476. 10.1093/jac/dkh346.CrossRefPubMed Stallmann HP, Faber C, Bronckers AL, Nieuw Amerongen AV, Wuisman PI: Osteomyelitis prevention in rabbits using antimicrobial peptide hLF1-11- or gentamicin-containing calcium phosphate cement. J Antimicrob Chemother. 2004, 54: 472-476. 10.1093/jac/dkh346.CrossRefPubMed
27.
go back to reference Baro M, Sanchez E, Delgado A, Perera A, Evora C: In vitro-in vivo characterization of gentamicin bone implants. J Control Release. 2002, 83: 353-10.1016/S0168-3659(02)00179-7.CrossRefPubMed Baro M, Sanchez E, Delgado A, Perera A, Evora C: In vitro-in vivo characterization of gentamicin bone implants. J Control Release. 2002, 83: 353-10.1016/S0168-3659(02)00179-7.CrossRefPubMed
28.
go back to reference Torrado S, Frutos P, Frutos G: Gentamicin bone cements: characterisation and release (in vitro and in vivo assays). Int J Pharm. 2001, 217: 57-69. 10.1016/S0378-5173(01)00587-7.CrossRefPubMed Torrado S, Frutos P, Frutos G: Gentamicin bone cements: characterisation and release (in vitro and in vivo assays). Int J Pharm. 2001, 217: 57-69. 10.1016/S0378-5173(01)00587-7.CrossRefPubMed
29.
go back to reference Nelson CL, McLaren SG, Skinner RA, Smeltzer MS, Thomas JR, Olsen KM: The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. J Orthop Res. 2002, 20: 643-647. 10.1016/S0736-0266(01)00133-4.CrossRefPubMed Nelson CL, McLaren SG, Skinner RA, Smeltzer MS, Thomas JR, Olsen KM: The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. J Orthop Res. 2002, 20: 643-647. 10.1016/S0736-0266(01)00133-4.CrossRefPubMed
Metadata
Title
In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile
Authors
Hein P Stallmann
Chris Faber
Antonius LJJ Bronckers
Arie V Nieuw Amerongen
Paul IJM Wuisman
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2006
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-7-18

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