Restorative Dentistry and Endodontics

The Korean Academy of Conservative Dentistry (대한치과보존학회)
권호 표지
DOI QR코드

DOI QR Code

Incorporation of amoxicillin-loaded microspheres in mineral trioxide aggregate cement: an in vitro study

  • Received : 2020.03.08
  • Accepted : 2020.05.26
  • Published : 2020.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: In this study, we investigated the potential of amoxicillin-loaded polymeric microspheres to be delivered to tooth root infection sites via a bioactive reparative cement. Materials and Methods: Amoxicillin-loaded microspheres were synthesized by a spray-dray method and incorporated at 2.5% and 5% into a mineral trioxide aggregate cement clinically used to induce a mineralized barrier at the root tip of young permanent teeth with incomplete root development and necrotic pulp. The formulations were modified in liquid:powder ratios and in composition by the microspheres. The optimized formulations were evaluated in vitro for physical and mechanical eligibility. The morphology of microspheres was observed under scanning electron microscopy. Results: The optimized cement formulation containing microspheres at 5% exhibited a delayed-release response and maintained its fundamental functional properties. When mixed with amoxicillin-loaded microspheres, the setting times of both test materials significantly increased. The diametral tensile strength of cement containing microspheres at 5% was similar to control. However, phytic acid had no effect on this outcome (p > 0.05). When mixed with modified liquid:powder ratio, the setting time was significantly longer than that original liquid:powder ratio (p < 0.05). Conclusions: Lack of optimal concentrations of antibiotics at anatomical sites of the dental tissues is a hallmark of recurrent endodontic infections. Therefore, targeting the controlled release of broad-spectrum antibiotics may improve the therapeutic outcomes of current treatments. Overall, these results indicate that the carry of amoxicillin by microspheres could provide an alternative strategy for the local delivery of antibiotics for the management of tooth infections.

Keywords

Acknowledgement

The authors gratefully acknowledge Microscopy and Microanalysis Center (Federal University of Rio Grande do Sul) for the microscopy analyses and Angelus for providing the MTA used in this research. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES)-Finance Code 001-scholarship.

References

  1. Ricucci D, Loghin S, Niu LN, Tay FR. Changes in the radicular pulp-dentine complex in healthy intact teeth and in response to deep caries or restorations: a histological and histobacteriological study. J Dent 2018;73:76-90.
  2. Ricucci D, Siqueira JF Jr, Loghin S, Lin LM. Pulp and apical tissue response to deep caries in immature teeth: a histologic and histobacteriologic study. J Dent 2017;56:19-32.
  3. Farges JC, Alliot-Licht B, Renard E, Ducret M, Gaudin A, Smith AJ, Cooper PR. Dental pulp defence and repair mechanisms in dental caries. Mediators Inflamm 2015;2015:230251.
  4. Martin FE. Carious pulpitis: microbiological and histopathological considerations. Aust Endod J 2003;29:134-137.
  5. Guerrero F, Mendoza A, Ribas D, Aspiazu K. Apexification: a systematic review. J Conserv Dent 2018;21:462-465.
  6. Flanagan TA. What can cause the pulps of immature, permanent teeth with open apices to become necrotic and what treatment options are available for these teeth. Aust Endod J 2014;40:95-100.
  7. Conde MCM, Chisini LA, Sarkis-Onofre R, Schuch HS, Nor JE, Demarco FF. A scoping review of root canal revascularization: relevant aspects for clinical success and tissue formation. Int Endod J 2017;50:860-874.
  8. Felippe WT, Felippe MCS, Rocha MJC. The effect of mineral trioxide aggregate on the apexification and periapical healing of teeth with incomplete root formation. Int Endod J 2006;39:2-9.
  9. Pace R, Giuliani V, Nieri M, Di Nasso L, Pagavino G. Mineral trioxide aggregate as apical plug in teeth with necrotic pulp and immature apices: a 10-year case series. J Endod 2014;40:1250-1254.
  10. Torabinejad M, Nosrat A, Verma P, Udochukwu O. Regenerative endodontic treatment or mineral trioxide aggregate apical plug in teeth with necrotic pulps and open apices: a systematic review and meta-analysis. J Endod 2017;43:1806-1820.
  11. Mohammadi Z, Shalavi S. Effect of hydroxyapatite and bovine serum albumin on the antibacterial activity of MTA. Iran Endod J 2011;6:136-139.
  12. Kim RJY, Kim MO, Lee KS, Lee DY, Shin JH. An in vitro evaluation of the antibacterial properties of three mineral trioxide aggregate (MTA) against five oral bacteria. Arch Oral Biol 2015;60:1497-1502.
  13. Piluso S, Soultan AH, Patterson J. Molecularly engineered polymer-based systems in drug deliver y and regenerative medicine. Curr Pharm Des 2017;23:281-294.
  14. Merkle HP. Drug deliver y's quest for polymers: where are the frontiers? Eur J Pharm Biopharm 2015;97:293-303.
  15. Cuppini M, Zatta KC, Mestieri LB, Grecca FS, Leitune VCB, Guterres SS, Collares FM. Antimicrobial and anti-inflammatory drug-delivery systems at endodontic reparative material: synthesis and characterization. Dent Mater 2019;35:457-467.
  16. Ghosh Dastidar D, Saha S, Chowdhury M. Porous microspheres: synthesis, characterisation and applications in pharmaceutical & medical fields. Int J Pharm 2018;548:34-48.
  17. Gupta V, Khan Y, Berkland CJ, Laurencin CT, Detamore MS. Microsphere-based scaffolds in regenerative engineering. Annu Rev Biomed Eng 2017;19:135-161.
  18. Chawla A, Sharma P, Pawar P. Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: formulation, optimization and in vitro evaluation. Acta Pharm 2012;62:529-545.
  19. Kaur G, Grewal J, Jyoti K, Jain UK, Chandra R, Madan J. Oral controlled and sustained drug delivery systems: concepts, advances, preclinical, and clinical status, In: Grumezescu AM, editor. Drug targeting and stimuli sensitive drug delivery systems. Norwich, NY: William Andrew Publishing; 2018. p567-626.
  20. Bolfoni MR, Pappen FG, Pereira-Cenci T, Jacinto RC. Antibiotic prescription for endodontic infections: a survey of Brazilian endodontists. Int Endod J 2018;51:148-156.
  21. Segura-Egea JJ, Gould K, Sen BH, Jonasson P, Cotti E, Mazzoni A, Sunay H, Tjaderhane L, Dummer PM. Antibiotics in endodontics: a review. Int Endod J 2017;50:1169-1184.
  22. Dornelles NB, Collares FM, Genari B, de Souza Balbinot G, Samuel SMW, Arthur RA, Visioli F, Guterres SS, Leitune VCB. Influence of the addition of microsphere load amoxicillin in the physical, chemical and biological properties of an experimental endodontic sealer. J Dent 2018;68:28-33.
  23. Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 2006;27:2907-2915.
  24. Ha WN, Nicholson T, Kahler B, Walsh LJ. Methodologies for measuring the setting times of mineral trioxide aggregate and Portland cement products used in dentistry. Acta Biomater Odontol Scand 2016;2:25-30.
  25. Parhizkar A, Nojehdehian H, Asgar y S. Triple antibiotic paste: momentous roles and applications in endodontics: a review. Restor Dent Endod 2018;43:e28.
  26. Lee G, Chung C, Kim S, Shin SJ. Observation of an extracted premolar 2.5 years after mineral trioxide aggregate apexification using micro-computed tomography. Restor Dent Endod 2019;45:e4.
  27. Cartagena AF, Esmerino LA, Polak-Junior R, Olivieri Parreiras S, Domingos Michel M, Farago PV, Campanha NH. New denture adhesive containing miconazole nitrate polymeric microparticles: antifungal, adhesive force and toxicity properties. Dent Mater 2017;33:e53-e61.
  28. Gavini E, Bonferoni MC, Rassu G, Obinu A, Ferrari F, Giunchedi P. Biodegradable microspheres as intravitreal deliver y systems for prolonged drug release. what is their eminence in the nanoparticle era? Curr Drug Deliv 2018;15:930-940.
  29. Duarte MA, Demarchi AC, Yamashita JC, Kuga MC, Fraga SC. pH and calcium ion release of 2 root-end filling materials. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:345-347.
  30. Javid B, Panahandeh N, Torabzadeh H, Nazarian H, Parhizkar A, Asgar y S. Bioactivity of endodontic biomaterials on dental pulp stem cells through dentin. Restor Dent Endod 2019;45:e3.
  31. Mestieri LB, Zaccara IM, Pinheiro LS, Barletta FB, Kopper PMP, Grecca FS. Cytocompatibility and cell proliferation evaluation of calcium phosphate-based root canal sealers. Restor Dent Endod 2019;45:e2.
  32. Fridland M, Rosado R. Mineral trioxide aggregate (MTA) solubility and porosity with different water-to-powder ratios. J Endod 2003;29:814-817.
  33. Basturk FB, Nekoofar MH, Gunday M, Dummer PM. The effect of various mixing and placement techniques on the compressive strength of mineral trioxide aggregate. J Endod 2013;39:111-114.
  34. Bouyarmane H, El Hanbali I, El Karbane M, Rami A, Saoiabi A, Saoiabi S, Masse S, Coradin T, Laghzizil A. Parameters influencing ciprofloxacin, ofloxacin, amoxicillin and sulfamethoxazole retention by natural and converted calcium phosphates. J Hazard Mater 2015;291:38-44.