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Antibiotic and anesthetic drug release from double-setting α-TCP cements

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Abstract

The alpha phase of tricalcium phosphate (α-TCP) can form calcium-deficient hydroxyapatite (CDHA), similar to bone hydroxyapatite. α-TCP can be employed as a biocompatible cement and used as a drug vehicle. Double-setting α-TCP cement composed of acrylamide (α-TCP DS) has better mechanical properties than traditional α-TCP cement. However, no studies on the use of α-TCP DS-based systems for drug release have been reported. In this study, we prepared α-TCP- and α-TCP DS-based samples containing gentamicin sulfate, lidocaine hydrochloride, bupivacaine hydrochloride and levobupivacaine hydrochloride. The properties of the samples were characterized, and the use of the samples as vehicles for these drugs was evaluated. The cements were characterized using X-ray diffraction, Fourier transform infrared spectroscopy, mechanical property tests and apparent porosity evaluation. The drug release in vitro was determined using ultraviolet–visible absorption spectroscopy. For statistical analysis, a confidence interval of 95% with a significance level < 5% was used. Neither the hydrogel nor the drugs interfered with the formation of CDHA, but they increased the mechanical strength of the studied cement. The Peppas–Sahlin model described the mechanisms involved in the drug-release kinetics process, revealing that Fickian diffusion was the main drug-release mechanism with a small influence from the Case II mechanism.

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References

  1. Carrodeguas RG, De Aza S (2011) α-Tricalcium phosphate: synthesis, properties and biomedical applications. Acta Biomater 7:3536–3546

    Article  Google Scholar 

  2. Verron E, Gauthier O, Janvier P, Le Guen H, Holopherne D, Cavagna R, Bouler JM (2010) Analgesic properties of calcium phosphate apatite loaded with bupivacaine on postoperative pain. J Biomed Mater Res B Appl Biomater 94:89–96

    Google Scholar 

  3. Ahn M-K, Moon Y-W, Koh Y-H, Kim H-E (2013) Production of highly porous triphasic calcium phosphate scaffolds with excellent in vitro bioactivity using vacuum-assisted foaming of ceramic suspension (VFC) technique. Ceram Int 39:5879–5885

    Article  Google Scholar 

  4. Dos Santos LA, Carrodeguas RG, Rogero SO, Higa OZ, Boschi AO, de Arruda AC (2002) α-Tricalcium phosphate cement: “in vitro” cytotoxicity. Biomaterials 23:2035–2042

    Article  Google Scholar 

  5. Dos Santos LA, de Oliveira LC, Rigo ECS, Carrodeguas RG, Boschi AO, de Arruda ACF (1999) Influence of polymeric additives on the mechanical properties of α-tricalcium phosphate cement. Bone 25:99S–102S

    Article  Google Scholar 

  6. Dos Santos LA, Carrodeguas RG, Boschi AO, Arruda AC (2003) Dual-setting calcium phosphate cement modified with ammonium polyacrylate. Artif Organs 27:412–418

    Article  Google Scholar 

  7. Oriá AP, Neto FAD, Laus JL, dos Santos LA, Piza ET, Brunelli AT, Nishimori CT, de Souza ALG (2006) Evaluation of a double-setting α-tricalcium phosphate cement in eviscerated rabbit eyes. Ophthal Plast Reconstr Surg 22:126–130

    Article  Google Scholar 

  8. Vallet-Regí M, Balas F, Colilla M, Manzano M (2008) Bone-regenerative bioceramic implants with drug and protein controlled delivery capability. Prog Solid State Chem 36:163–191

    Article  Google Scholar 

  9. Aragón J, González R, Fuentes G, Palin L, Croce G, Viterbo D (2012) In vitro release kinetics and physical, chemical and mechanical characterization of a POVIAC®/CaCO3/HAP-200 composite. J Mater Sci Mater Med 23:259–270

    Article  Google Scholar 

  10. Sugo K, Kawashima R, Nakasu M, Nakajima T (2016) Antibiotic elution profile and physical properties of a novel calcium phosphate cement material. J Ceram Soc Jpn 124:954–958

    Article  Google Scholar 

  11. Zalavras CG, Patzakis MJ, Holtom P (2004) Local antibiotic therapy in the treatment of open fractures and osteomyelitis. Clin Orthop Relat Res 427:86–93

    Article  Google Scholar 

  12. Bond DM, Rudan J, Kobus SM, Adams MA (2004) Depot local anesthetic in polymethylmethacrylate bone cement. A preliminary study. Clin Orthop Relat Res 418:242–245

    Article  Google Scholar 

  13. Giordano V, Rios H, Moreirão M, Giordano M, Amaral NP, Pallottino A, Oliveira S (2007) Ensaio mecânico da resistência ao impacto do cimento ósseo puro e associado a duas drogas anestésicas locais. Rev Bras Ortop 42:225–230

    Article  Google Scholar 

  14. Rang H, Ritter JM, Flower R, Henderson G (2015) Rang and Dale’s pharmacology, 8th edn. Elsevier, Edinburgh

    Google Scholar 

  15. Driessens FCM, Fernández E, Ginebra MP, Boltong MG, Planell JA (1997) Calcium phosphates and ceramic bone cements vs. acrylic cements. Springer, Anales de Química, vol 93, pp 38–43. ISSN : 1130–2283

  16. Espanol M, Perez RA, Montufar EB, Marichal C, Sacco A, Ginebra MP (2009) Intrinsic porosity of calcium phosphate cements and its significance for drug delivery and tissue engineering applications. Acta Biomater 5:2752–2762

    Article  Google Scholar 

  17. Fernandes BL, Colpo JC, Manffra EF, Nohama P (2008) Biocompatible glassceramic applied in drug release system. Rev Bras Eng Biomed 24:33–37

    Article  Google Scholar 

  18. Paavola A, Yliruusi J, Kajimoto Y, Kalso E, Wahlström T, Rosenberg P (1995) Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block. Pharm Res 12:1997–2002

    Article  Google Scholar 

  19. Higuchi T (1963) Mechanism of sustained-action medication. theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 52:1145–1149

    Article  Google Scholar 

  20. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35

    Article  Google Scholar 

  21. Peppas NA, Sahlin JJ (1989) A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm 57:169–172

    Article  Google Scholar 

  22. Cirillo G, Spataro T, Curcio M, Spizzirri UG, Nicoletta FP, Picci N, Iemma F (2015) Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies. Mater Sci Eng C 48:499–510

    Article  Google Scholar 

  23. Duncan J, MacDonald JF, Hanna JV, Shirosaki Y, Hayakawa S, Osaka A, Skakle JMS, Gibson IR (2014) The role of the chemical composition of monetite on the synthesis and properties of α-tricalcium phosphate. Mater Sci Eng C 34:123–129

    Article  Google Scholar 

  24. Machado JLM, Giehl IC, Nardi NB, dos Santos LA (2011) Evaluation of scaffolds based on α-tricalcium phosphate cements for tissue engineering applications. IEEE Trans Bio-med Eng 58:1814–1819

    Article  Google Scholar 

  25. Vasconcellos LA, dos Santos LA (2013) Calcium phosphate cement scaffolds with PLGA fibers. Mater Sci Eng C 33:1032–1040

    Article  Google Scholar 

  26. Hurle K, Christel T, Gbureck U, Claus M, Juergen N, Friedlinde G-N (2016) Reaction kinetics of dual setting α-tricalcium phosphate cements. J Mater Sci Mater Med 27:1–13

    Article  Google Scholar 

  27. Fernandes JM, Coelho WT, Thürmer MB, Vieira RS, Santos LA (2012) Properties of calcium phosfate cement with addition of dispersant and hydrogel. Mater Sci Forum 727–28:1170–1174

    Article  Google Scholar 

  28. Beruto DT, Mezzasalma SA, Capurro M, Botter R, Cirillo P (2000) Use of α-tricalcium phosphate (TCP) as powders and as an aqueous dispersion to modify processing, microstructure, and mechanical properties of polymethylmethacrylate (PMMA) bone cements and to produce bone-substitute compounds. J Biomed Mater Res 49:498–505

    Article  Google Scholar 

  29. Marc Bohner M, Lemaître J, Van Landuyt P, Zambelli PY, Merkle HP, Gander B (1997) Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system. J Pharm Sci 86:565–572

    Article  Google Scholar 

  30. Ginebra MP, Traykova T, Planell JA (2006) Calcium phosphate cements as bone drug delivery systems: a review. J Control Release 113:102–110

    Article  Google Scholar 

  31. Wang F-J, Yang Y-Y, Zhang X-Z, Zhu X, Chung T-S, Moochhala S (2002) Cellulose acetate membranes for transdermal delivery of scopolamine base. Mater Sci Eng C 20:93–100

    Article  Google Scholar 

  32. Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42

    Article  Google Scholar 

  33. Demarchi CA, Debrassi A, Buzzi FC et al (2014) A magnetic nanogel based on O-carboxymethylchitosan for antitumor drug delivery: synthesis, characterization and in vitro drug release. Soft Matter 10:3441–3450

    Article  Google Scholar 

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Correspondence to Julio C. Colpo.

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Colpo, J.C., Pigatto, C., Brizuela, N. et al. Antibiotic and anesthetic drug release from double-setting α-TCP cements. J Mater Sci 53, 7112–7124 (2018). https://doi.org/10.1007/s10853-018-2071-4

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  • DOI: https://doi.org/10.1007/s10853-018-2071-4

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