Nonstoichiometric Hydroxyapatite-Anionic Collagen Composite as Support for the Double Sustained Release of Gentamicin and Norfloxacin/Ciprofloxacin

Virginia Conceição Amaro Martins

Department of Chemistry and Molecular Physics, Institute of Chemistry of São Carlos–University of São Paulo,
São Carlos, SP, Brazil

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Gilberto Goissis,

Gilberto Goissis

Department of Chemistry and Molecular Physics, Institute of Chemistry of São Carlos–University of São Paulo,
São Carlos, SP, Brazil

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Virginia Conceição Amaro Martins,

Virginia Conceição Amaro Martins

Department of Chemistry and Molecular Physics, Institute of Chemistry of São Carlos–University of São Paulo,
São Carlos, SP, Brazil

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Gilberto Goissis,

Gilberto Goissis

Department of Chemistry and Molecular Physics, Institute of Chemistry of São Carlos–University of São Paulo,
São Carlos, SP, Brazil

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First published: 24 December 2001

https://doi.org/10.1046/j.1525-1594.2000.06517.x

Citations: 38

Address correspondence and reprint requests to Dr. Gilberto Goissis, Departamento Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São Paulo, Av. Dr. Carlos Botelho, 1465, Cx. P. 780, São Carlos, CEP 13560–970, SP, Brazil. E-mail: [email protected]

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Abstract

Abstract: This work studied the sustained release of ciprofloxacin or norfloxacin and gentamicin from nonstoichiometric hydroxyapatite (nHA) and anionic collagen composite. Within the first 24 and 48 h, the total antibiotic supply was significantly higher than the minimal inhibitory concentration required for the majority of the gram-negative bacteria. Although gentamicin was completely released from the matrix after 48 h by a normal diffusion mechanism, ciprofloxacin or norfloxacin release was characterized by a 2-phase release mechanism due to binding to nHA by complexation with calcium ion. Under the conditions studied, most of the norfloxacin or ciprofloxacin only will be disposable due to bioresorption or dissociation of the complexes. In conclusion, due to its biocompatibility nHA-anionic collagen composite may be a convenient support for the double sustained release of the antibiotics gentamicin and ciprofloxacin/norfloxacin for the control of bone infection while promoting bone tissue growth.

REFERENCES

1 Ostermann PA, Henry SL, Seligson D. The role of local antibiotic therapy in the management of compound fractures. Clin Orthop Rel Res 1993; 295: 102 11.
PubMed Web of Science® Google Scholar
2 Price JS, Tencer AF, Arm DM, Bohach GA. Controlled release of antibiotics from coated orthopedic implants. J Biomed Mater Res 1996; 30: 281 6.
10.1002/(SICI)1097-4636(199603)30:3<281::AID-JBM2>3.0.CO;2-M
CAS PubMed Web of Science® Google Scholar
3 Becker PL, Smith RA, Williams RS, Dutkowsky JPJ. Comparison of antibiotic release from polymethylmethacrylate beads and collagen sponge. Orthop Res 1994; 12: 737 41.
10.1002/jor.1100120517
CAS PubMed Web of Science® Google Scholar
4 Sorensen TS, Sorensen AI, Merser S. Rapid release of gentamicin from collagen sponge: In vitro comparison with plastic beads. Acta Orthop Scand 1990; 61: 353 6.
10.3109/17453679008993535
CAS PubMed Web of Science® Google Scholar
5 Itokazu M, Matsunaga T, Kumazawa S, Yang W. A novel drug delivery system for osteomyelitis using porous hydroxyapatite blocks loaded by centrifugation. J Appl Biomater 1995; 6: 167 9.
10.1002/jab.770060304
CAS PubMed Web of Science® Google Scholar
6 Hamanishi C, Kitamoto K, Tanaka S. A self-hardening TTCP-DCPD apatite cement for release of vancomycin. J Biomed Mater Res 1996; 33: 139 43.
10.1002/(SICI)1097-4636(199623)33:3<139::AID-JBM3>3.0.CO;2-R
CAS PubMed Web of Science® Google Scholar
7 Salvati EA, Callaghan JJ, Brause BD, Klein RF, Small RD. Reimplantation in infection: Elution of gentamicin from cements and beads. Clin Orthop 1986; 207: 83 93.
PubMed Web of Science® Google Scholar
8 Teupe C, Meffert R, Winckler S. Ciprofloxacin impregnated poly-L-lactic acid drug carrier. Arch Orthop Trauma Surg 1992; 112: 33 5.
10.1007/BF00431041
CAS PubMed Web of Science® Google Scholar
9 Kurashina K, Kurita H, Kotani A, Takeuchi H, Hirano, M. In vivo study of a calcium phosphate cement consisting of α-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide. Biomaterials 1997; 18: 147 51.
10.1016/S0142-9612(96)00173-1
CAS PubMed Web of Science® Google Scholar
10 Gao TJ, Lindholm TS, Kommonen B, Ragni P, Paronzini A, Lindholm TC. Microscopic evaluation of bone-implant contact between hydroxyapatite, bioactive glass, and tricalcium phosphate implanted in sheep diaphyseal defects. Biomaterials 1995; 16: 1175 9.
10.1016/0142-9612(95)93583-Y
CAS PubMed Web of Science® Google Scholar
11 Flautre B, Pasquier G, Blary MC. Evaluation of hydroxyapatite powder coated with collagen as an injectable bone substitute: Microscopic study in rabbits. J Mater Sci Mater Med 1996; 7: 63 7.
10.1007/BF00058716
CAS Web of Science® Google Scholar
12 Domb AJ, Manor N, Elmalak O. Biodegradable bone cement compositions based on acrylate and epoxide terminated poly(propylene fumarate) oligomers and calcium salt compositions. Biomaterials 1996; 17: 411 7.
10.1016/0142-9612(96)89657-8
CAS PubMed Web of Science® Google Scholar
13 Cirelli JA, Marcantonio E Jr, Marcantonio RAC, Lia RCC, Rossa C Jr, Goissis G. Regeneration of periodontal tissue in class II furcation by anionic collagen membrane barriers: A histometric analysis in dogs. Biomaterials (in press).
Google Scholar
14 Martins VCA, Goissis G, Ribeiro ACC, Bet MR. The controlled release of antibiotic by anionic collagen:calcium phosphate salts composites. Artif Organs 1998; 22: 215 21.
10.1046/j.1525-1594.1998.06004.x
CAS PubMed Web of Science® Google Scholar
15 Wallis, SC, Charles BG, Gahan LR, Filippich, LJ, Megan GB, Duckworth PA. Interaction of norfloxacin with divalent and trivalent pharmaceutical cations: In vitro complexation and in vivo pharmacokinetic studies in the dog. J Pharm Sci 1996; 85: 803 9.
10.1021/js960087f
CAS PubMed Web of Science® Google Scholar
16 Goissis G, Plepis AMG, Rocha JL. Processo de extração de colágeno de tecidos animais com auxílio de solventes orgânicos e meio alcalino. Patente BR PI 9.405.043–0, 1994.
Google Scholar
17 Jarcho M, Bolen CH, Thomas MB, Bobick J, Kay JF, Doremus RH. Hydroxylapatite synthesis and characterization in dense polycrystalline form. J Mat Sci 1976; 11: 2027 35.
CAS Web of Science® Google Scholar
18 Murphy J & Riley JP. A modified single solution method for the determination of phosphate in natural waters. Anal Chim Acta 1962; 27: 31 6.
10.1016/S0003-2670(00)88444-5
CAS PubMed Google Scholar
19 Vogel AI. Análise Inorgânica Quantitativa, 4th ed. Rio de Janeiro: Guanabara Dois, 1982.
Google Scholar
20 Silvester MF, Yannas IV, Forbes MJ. Collagen banded fibril structure and the collagen platelet reaction. Thromb Res 1989; 55: 135 48.
10.1016/0049-3848(89)90463-5
PubMed Web of Science® Google Scholar
21 Ryan JA. Colorimetric determination of gentamicin, kanamycin, tobramycin, and amikacin aminoglycosides with 2,4-dinitrofluorbenzene. J Pharm Sci 1984; 73: 1301 2.
10.1002/jps.2600730930
CAS PubMed Web of Science® Google Scholar
22 Yubao L, Klein CP, Zhang X, De Groot K. Formation of a bond apatite-like layer on the surface of porous hydroxyapatite ceramics. Biomaterials 1994; 15: 835 41.
10.1016/0142-9612(94)90039-6
CAS PubMed Google Scholar
23 Flandin F, Buffevant C, Herbage D. A differential scanning calorimetry analysis of the age-related changes in the thermal stability of rat skin collagen. Biochim Biophys Acta 1984; 791: 205 13.
10.1016/0167-4838(84)90010-4
CAS PubMed Web of Science® Google Scholar
24 Bohner M, Lemaitre J, Landuyt PV, Zambelli PY, Merkle HP, Gander B. Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system. J Pharm Sci 1997; 86: 565 72.
10.1021/js960405a
CAS PubMed Web of Science® Google Scholar
25 Sousa MH. Estudos de incorporação e liberação de antibióticos em membranas de colágeno. Dissertação, DQFM-IQSC-USP, 1998.
Google Scholar
26 Daly CC, Hoffman I, Hobbs M, Maida M, Zimba D, Davis R, Mughogho G, Cohen MS. Development of an antimicrobial susceptibility surveillance system for Neisseria gonorrhoeae in Malawi: Comparison of methods. J Clin Microbiol 1997; 35: 2985 8.
CAS PubMed Web of Science® Google Scholar
27 Putnan SD, Lavin BS, Stone JR, Oldfield Ec III, Hooper DG. Evaluation of standardized disk diffusion and agar dilution antibiotic susceptibility test methods by using strains of Neisseria gonorrhoeae from the United States and Southeast Asia. J Clin Microbiol 1992; 30: 974 80.
PubMed Web of Science® Google Scholar
28 Otsuka M, Matsuda Y, Yoshiko S, Fox JL, Higushi WI. A novel skeletal drug-delivery system using self-setting calcium phosphate cement: 3. Physicochemical properties and drug-release rate of bovine insulin and bovine albumin. J Pharm Sci 1994; 83: 255 8.
10.1002/jps.2600830229
PubMed Web of Science® Google Scholar

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Volume24, Issue3

March 2000

Pages 224-230

Nonstoichiometric Hydroxyapatite-Anionic Collagen Composite as Support for the Double Sustained Release of Gentamicin and Norfloxacin/Ciprofloxacin

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Nonstoichiometric Hydroxyapatite-Anionic Collagen Composite as Support for the Double Sustained Release of Gentamicin and Norfloxacin/Ciprofloxacin

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