Skip to main content

Advertisement

SpringerLink
Log in

Should local drug delivery systems be used in dentistry?

  • Review Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

In dentistry, the use of biomaterial-based drug delivery systems (DDS) aiming the release of the active compounds directly to the site of action is slowly getting more awareness among the scientific and medical community. Emerging technologies including nanotechnological platforms are offering novel approaches, but the majority are still in the proof-of-concept stage. This study critically reviews the potential use of DDS in anesthesiology, oral diseases, cariology, restorative dentistry, periodontics, endodontics, implantology, fixed and removable prosthodontics, and orthodontics with a special focus on infections. It also stresses the gaps and challenges faced. Despite numerous clinical and pharmacological advantages, some disadvantages of DDS pose an obstacle to their widespread use. The biomaterial’s biofunctionality may be affected when the drug is incorporated and may cause an additional risk of toxicity. Also, the release of sub-therapeutic levels of drugs such as antibiotics may lead to microbial resistance. Multiple available techniques for the manufacture of DDS may affect drug release profiles and their bioavailability. If the benefits outweigh the costs, DDS may be potentially used to prevent or treat oral pathologies as an alternative to conventional strategies. A case-by-case approach must be followed.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Langer R, Tirrell DA. Designing materials for biology and medicine. Nature. 2004;428(6982):487–92.

    Article  CAS  PubMed  Google Scholar 

  2. von Recum AF, LaBerge M. Educational goals for biomaterials science and engineering: prospective view. J Appl Biomater. 1995;6(2):137–44.

    Article  Google Scholar 

  3. Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161–77.

    Article  CAS  PubMed  Google Scholar 

  4. Singh R, Vyas SP. Topical liposomal system for localized and controlled drug delivery. J Dermatol Sci. 1996;13(2):107–11.

    Article  CAS  PubMed  Google Scholar 

  5. Ghosh P, Han G, De M, et al. Gold nanoparticles in delivery applications. Adv Drug Deliv Rev. 2008;60(11):1307–15.

    Article  CAS  PubMed  Google Scholar 

  6. Vilar G, Tulla-Puche J, Albericio F. Polymers and drug delivery systems. Curr Drug Deliv. 2012;9(4):367–94.

    Article  CAS  PubMed  Google Scholar 

  7. Kim S, Kim JH, Jeon O, et al. Engineered polymers for advanced drug delivery. Eur J Pharm Biopharm. 2009;71(3):420–30.

    Article  CAS  PubMed  Google Scholar 

  8. Anil S, Al-Sulaimani AF, Beeran AE, et al. Drug delivery systems in bone regeneration and implant dentistry, in Current concepts in dental implantology, I. Turkyilmaz, Editor. 2015;239–264.

  9. Da Rocha HA, Silva CF, Santiago FL, et al. Local drug delivery systems in the treatment of periodontitis: a literature review. J Int Acad Periodontol. 2015;17(3):82–90.

    PubMed  Google Scholar 

  10. Lee PI, Li J-X. Evolution of oral controlled release dosage forms, in Oral controlled release formulation design and drug delivery, H. Wen and K. Park, Editors. 2010;21–31.

  11. Rasmussen N. America’s first amphetamine epidemic 1929–1971: a quantitative and qualitative retrospective with implications for the present. Am J Public Health. 2008;98(6):974–85.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Joshi D, Garg T, Goyal AK, et al. Advanced drug delivery approaches against periodontitis. Drug Deliv. 2016;23(2):363–77.

    Article  CAS  PubMed  Google Scholar 

  13. Bettencourt AF, Neves CB, de Almeida MS, et al. Biodegradation of acrylic based resins: A review. Dent Mater. 2010;26(5):e171–80.

    Article  CAS  PubMed  Google Scholar 

  14. Li B, Webster TJ. Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopaedic infections J Orthop Res. 2018;36(1):22–32.

    PubMed  Google Scholar 

  15. Banting DW, Hill SA. Microwave disinfection of dentures for the treatment of oral candidiasis. Spec Care Dentist. 2001;21(1):4–8.

    Article  CAS  PubMed  Google Scholar 

  16. Taware CP, Mazumdar S, Pendharkar M, et al. A bioadhesive delivery system as an alternative to infiltration anesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(6):609–15.

    Article  CAS  PubMed  Google Scholar 

  17. Salim N, Moore C, Silikas N, et al. Fungicidal amounts of antifungals are released from impregnated denture lining material for up to 28 days. J Dent. 2012;40(6):506–12.

    Article  CAS  PubMed  Google Scholar 

  18. Bueno MG, Urban VM, Barberio GS, et al. Effect of antimicrobial agents incorporated into resilient denture relines on the Candida albicans biofilm. Oral Dis. 2015;21(1):57–65.

    Article  CAS  PubMed  Google Scholar 

  19. Puri K, Puri N. Local drug delivery agents as adjuncts to endodontic and periodontal therapy. J Med Life. 2013;6(4):414–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Coelho JF, Ferreira PC, Alves P, et al. Drug delivery systems: advanced technologies potentially applicable in personalized treatments. EPMA J. 2010;1(1):164–209.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bertolini MM, Portela MB, Curvelo JA, et al. Resins-based denture soft lining materials modified by chlorhexidine salt incorporation: an in vitro analysis of antifungal activity, drug release and hardness. Dent Mater. 2014;30(8):793–8.

    Article  CAS  PubMed  Google Scholar 

  22. Lima JF, Maciel JG, Hotta J, et al. Porosity of temporary denture soft liners containing antifungal agents. J Appl Oral Sci. 2016;24(5):453–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Farrugia C, Camilleri J. Antimicrobial properties of conventional restorative filling materials and advances in antimicrobial properties of composite resins and glass ionomer cements-A literature review. Dent Mater. 2015;31(4):e89-99.

    Article  CAS  PubMed  Google Scholar 

  24. Alvarez-lorenzo C, Concheiro A. Drug/medical device combination products with stimuli-responsive eluting surface, in Smart Materials For Drug Delivery: Volume 2, C. Alvarez-Lorenzo and A. Concheiro, Editors. 2013;313–348.

  25. Imazato S. Antibacterial properties of resin composites and dentin bonding systems. Dent Mater. 2003;19(6):449–57.

    Article  CAS  PubMed  Google Scholar 

  26. Coimbra P. Preparação e Caracterização de Sistemas de Libertação Controlada de Fármacos com base em Polímeros de Origem Natural. Coimbra: Faculdade de Ciências e Tecnologia da Universidade de Coimbra; 2010.

    Google Scholar 

  27. Huynh CT, Lee D-S. Controlled release, in Encyclopedia of polymeric nanomaterials, K. Müllen and S. Kobayashi, Editors. 2014;1–12.

  28. Carr MP, Horton JE. Evaluation of a transoral delivery system for topical anesthesia. J Am Dent Assoc. 2001;132(12):1714–9.

    Article  CAS  PubMed  Google Scholar 

  29. Carr MP, Horton JE. Clinical evaluation and comparison of 2 topical anesthetics for pain caused by needle sticks and scaling and root planing. J Periodontol. 2001;72(4):479–84.

    Article  CAS  PubMed  Google Scholar 

  30. Franz-Montan M, Ribeiro LNM, Volpato MC, et al. Recent advances and perspectives in topical oral anesthesia. Expert Opin Drug Deliv. 2017;14(5):673–84.

    Article  CAS  PubMed  Google Scholar 

  31. Paphangkorakit J, Sangsirinakagul C, Priprem A. Relief of palatal injection pain by liposome-encapsulated 2% lignocaine prepared by ultrasonic dental scaler. Br J Oral Maxillofac Surg. 2012;50(8):784–7.

    Article  PubMed  Google Scholar 

  32. Franz-Montan M, de Paula E, Groppo FC, et al. Liposomal delivery system for topical anaesthesia of the palatal mucosa. Br J Oral Maxillofac Surg. 2012;50(1):60–4.

    Article  CAS  PubMed  Google Scholar 

  33. Franz-Montan M, Baroni D, Brunetto G, et al. Liposomal lidocaine gel for topical use at the oral mucosa: characterization, in vitro assays and in vivo anesthetic efficacy in humans. J Liposome Res. 2015;25(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  34. Gaeta GM, Gombos F, Femiano F, et al. Acitretin and treatment of the oral leucoplakias. A model to have an active molecules release. J Eur Acad Dermatol Venereol. 2000;14(6): 473–8.

  35. Piattelli A, Fioroni M, Santinelli A, et al. bcl-2 expression and apoptotic bodies in 13-cis-retinoic acid (isotretinoin)-topically treated oral leukoplakia: a pilot study. Oral Oncol. 1999;35(3):314–20.

    Article  CAS  PubMed  Google Scholar 

  36. Senel S, Kremer MJ, Kas S, et al. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials. 2000;21(20):2067–71.

    Article  CAS  PubMed  Google Scholar 

  37. Thongprasom K, Dhanuthai K. Steriods in the treatment of lichen planus: a review. J Oral Sci. 2008;50(4):377–85.

    Article  CAS  PubMed  Google Scholar 

  38. Vazquez JA, Patton LL, Epstein JB, et al. Randomized, comparative, double-blind, double-dummy, multicenter trial of miconazole buccal tablet and clotrimazole troches for the treatment of oropharyngeal candidiasis: study of miconazole Lauriad(R) efficacy and safety (SMiLES). HIV Clin Trials. 2010;11(4):186–96.

    Article  CAS  PubMed  Google Scholar 

  39. Karlsmark T, Goodman JJ, Drouault Y, et al. Randomized clinical study comparing Compeed cold sore patch to acyclovir cream 5% in the treatment of herpes simplex labialis. J Eur Acad Dermatol Venereol. 2008;22(10):1184–92.

    Article  CAS  PubMed  Google Scholar 

  40. Woo SB, Challacombe SJ. Management of recurrent oral herpes simplex infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(Suppl 12):e1-18.

    Google Scholar 

  41. Meurman JH. Probiotics: do they have a role in oral medicine and dentistry? Eur J Oral Sci. 2005;113(3):188–96.

    Article  PubMed  Google Scholar 

  42. Heir G, Karolchek S, Kalladka M, et al. Use of topical medication in orofacial neuropathic pain: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(4):466–9.

    Article  PubMed  Google Scholar 

  43. Imfeld T. Chewing gum–facts and fiction: a review of gum-chewing and oral health. Crit Rev Oral Biol Med. 1999;10(3):405–19.

    Article  CAS  PubMed  Google Scholar 

  44. Dodds MW, Chidichimo D, Haas MS. Delivery of active agents from chewing gum for improved remineralization. Adv Dent Res. 2012;24(2):58–62.

    Article  CAS  PubMed  Google Scholar 

  45. Rijkers GT, de Vos WM, Brummer RJ, et al. Health benefits and health claims of probiotics: bridging science and marketing. Br J Nutr. 2011;106(9):1291–6.

    Article  CAS  PubMed  Google Scholar 

  46. Caglar E, Cildir SK, Ergeneli S, et al. Salivary mutans streptococci and lactobacilli levels after ingestion of the probiotic bacterium Lactobacillus reuteri ATCC 55730 by straws or tablets. Acta Odontol Scand. 2006;64(5):314–8.

    Article  PubMed  Google Scholar 

  47. Caglar E, Kavaloglu SC, Kuscu OO, et al. Effect of chewing gums containing xylitol or probiotic bacteria on salivary mutans streptococci and lactobacilli. Clin Oral Investig. 2007;11(4):425–9.

    Article  CAS  PubMed  Google Scholar 

  48. Moraschini V, Fai CK, Alto RM, et al. Amalgam and resin composite longevity of posterior restorations: A systematic review and meta-analysis. J Dent. 2015;43(9):1043–50.

    Article  CAS  PubMed  Google Scholar 

  49. Wang Z, Shen Y, Haapasalo M. Dental materials with antibiofilm properties. Dent Mater. 2014;30(2):e1-16.

    Article  CAS  PubMed  Google Scholar 

  50. Schmalz G, Ergucu Z, Hiller KA. Effect of dentin on the antibacterial activity of dentin bonding agents. J Endod. 2004;30(5):352–8.

    Article  CAS  PubMed  Google Scholar 

  51. Busscher HJ, Rinastiti M, Siswomihardjo W, et al. Biofilm formation on dental restorative and implant materials. J Dent Res. 2010;89(7):657–65.

    Article  CAS  PubMed  Google Scholar 

  52. Nedeljkovic I, Teughels W, De Munck J, et al. Is secondary caries with composites a material-based problem? Dent Mater. 2015;31(11):e247–77.

    Article  CAS  PubMed  Google Scholar 

  53. Imazato S, Kinomoto Y, Tarumi H, et al. Antibacterial activity and bonding characteristics of an adhesive resin containing antibacterial monomer MDPB. Dent Mater. 2003;19(4):313–9.

    Article  CAS  PubMed  Google Scholar 

  54. Jedrychowski JR, Caputo AA, Kerper S. Antibacterial and mechanical properties of restorative materials combined with chlorhexidines. J Oral Rehabil. 1983;10(5):373–81.

    Article  CAS  PubMed  Google Scholar 

  55. Hiraishi N, Yiu CK, King NM, et al. Chlorhexidine release and water sorption characteristics of chlorhexidine-incorporated hydrophobic/hydrophilic resins. Dent Mater. 2008;24(10):1391–9.

    Article  CAS  PubMed  Google Scholar 

  56. Zhang JF, Wu R, Fan Y, et al. Antibacterial dental composites with chlorhexidine and mesoporous silica. J Dent Res. 2014;93(12):1283–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Luo D, Shahid S, Hasan SM, et al. Controlled release of chlorhexidine from a HEMA-UDMA resin using a magnetic field. Dent Mater. 2018;34(5):764–75.

    Article  CAS  PubMed  Google Scholar 

  58. Ehara A, Torii M, Imazato S, et al. Antibacterial activities and release kinetics of a newly developed recoverable controlled agent-release system. J Dent Res. 2000;79(3):824–8.

    Article  CAS  PubMed  Google Scholar 

  59. Othman HF, Wu CD, Evans CA, et al. Evaluation of antimicrobial properties of orthodontic composite resins combined with benzalkonium chloride. Am J Orthod Dentofacial Orthop. 2002;122(3):288–94.

    Article  PubMed  Google Scholar 

  60. Sehgal V, Shetty VS, Mogra S, et al. Evaluation of antimicrobial and physical properties of orthodontic composite resin modified by addition of antimicrobial agents–an in-vitro study. Am J Orthod Dentofacial Orthop. 2007;131(4):525–9.

    Article  PubMed  Google Scholar 

  61. Saito K, Hayakawa T, Kawabata R, et al. In vitro antibacterial and cytotoxicity assessments of an orthodontic bonding agent containing benzalkonium chloride. Angle Orthod. 2009;79(2):331–7.

    Article  PubMed  Google Scholar 

  62. Rathke A, Staude R, Muche R, et al. Antibacterial activity of a triclosan-containing resin composite matrix against three common oral bacteria. J Mater Sci Mater Med. 2010;21(11):2971–7.

    Article  CAS  PubMed  Google Scholar 

  63. Wicht MJ, Haak R, Kneist S, et al. A triclosan-containing compomer reduces Lactobacillus spp. predominant in advanced carious lesions. Dent Matet. 2005;21(9): 831–6.

  64. de Souza Araujo IJ, de Paula AB, Bruschi Alonso RC, et al. A novel Triclosan Methacrylate-based composite reduces the virulence of Streptococcus mutans biofilm. Plos one. 2018;13(4): e0195244.

  65. Zeng P, Rao A, Wiedmann TS, et al. Solubility properties of chlorhexidine salts. Drug Dev Ind Pharm. 2009;35(2):172–6.

    Article  CAS  PubMed  Google Scholar 

  66. Imazato S, Chen J-h, Ma S, et al. Antibacterial resin monomers based on quaternary ammonium and their benefits in restorative dentistry. Jpn Dent Sci Rev. 2012;48(2): 115–125.

  67. Cocco AR, Rosa WL, Silva AF, et al. A systematic review about antibacterial monomers used in dental adhesive systems: Current status and further prospects. Dent Mater. 2015;31(11):1345–62.

    Article  CAS  PubMed  Google Scholar 

  68. Cheng L, Weir MD, Xu HH, et al. Effect of amorphous calcium phosphate and silver nanocomposites on dental plaque microcosm biofilms. J Biomed Mater Res B Appl Biomater. 2012;100(5):1378–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Niu LN, Fang M, Jiao K, et al. Tetrapod-like zinc oxide whisker enhancement of resin composite. J Dent Res. 2010;89(7):746–50.

    Article  CAS  PubMed  Google Scholar 

  70. Tavassoli Hojati S, Alaghemand H, Hamze F, et al. Antibacterial, physical and mechanical properties of flowable resin composites containing zinc oxide nanoparticles. Dent Mater. 2013;29(5):495–505.

    Article  CAS  PubMed  Google Scholar 

  71. Stanislawczuk R, Reis A, Loguercio AD. A 2-year in vitro evaluation of a chlorhexidine-containing acid on the durability of resin-dentin interfaces. J Dent. 2011;39(1):40–7.

    Article  CAS  PubMed  Google Scholar 

  72. Yiu CK, Hiraishi N, Tay FR, et al. Effect of chlorhexidine incorporation into dental adhesive resin on durability of resin-dentin bond. J Adhes Dent. 2012;14(4):355–62.

    CAS  PubMed  Google Scholar 

  73. Pomacondor-Hernandez C, Antunes AN, Hipolito V, et al. Effect of replacing a component of a self-etch adhesive by chlorhexidine on bonding to dentin. Braz Dent J. 2013;24(4):335–9.

    Article  PubMed  Google Scholar 

  74. Xiao YH, Ma S, Chen JH, et al. Antibacterial activity and bonding ability of an adhesive incorporating an antibacterial monomer DMAE-CB. J Biomed Mater Res B Appl Biomater. 2009;90(2):813–7.

    Article  CAS  PubMed  Google Scholar 

  75. Zhang L, Yuan CY, Tian FC, et al. Antibacterial effect of self-etching adhesive systems on Streptococcus mutans. Beijing Da Xue Xue Bao Yi Xue Ban. 2016;48(1):57–62.

    CAS  PubMed  Google Scholar 

  76. Inagaki LT, Dainezi VB, Alonso RC, et al. Evaluation of sorption/solubility, softening, flexural strength and elastic modulus of experimental resin blends with chlorhexidine. J Dent. 2016;49:40–5.

    Article  CAS  PubMed  Google Scholar 

  77. Frencken JE, Van 't Hof MA, Van Amerongen WE, et al. Effectiveness of single-surface ART restorations in the permanent dentition: a meta-analysis. J Dent Res. 2004;83(2): 120–3.

  78. Ferreira JM, Pinheiro SL, Sampaio FC, et al. Use of glass ionomer cement containing antibiotics to seal off infected dentin: a randomized clinical trial. Braz Dent J. 2013;24(1):68–73.

    Article  PubMed  Google Scholar 

  79. Yesilyurt C, Er K, Tasdemir T, et al. Antibacterial activity and physical properties of glass-ionomer cements containing antibiotics. Oper Dent. 2009;34(1):18–23.

    Article  PubMed  Google Scholar 

  80. Prabhakar AR, Prahlad D, Kumar SR. Antibacterial activity, fluoride release, and physical properties of an antibiotic-modified glass ionomer cement. Pediatr Dent. 2013;35(5):411–5.

    CAS  PubMed  Google Scholar 

  81. Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm. 2000;50(1):83–99.

    Article  CAS  PubMed  Google Scholar 

  82. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol. 2000;2002(28):12–55.

    Google Scholar 

  83. Greenstein G, Tonetti M. The role of controlled drug delivery for periodontitis. The Research, Science and Therapy Committee of the American Academy of Periodontology. J Periodontol. 2000;71(1): 125–40.

  84. Sousa FF, Luzardo-Alvarez A, Perez-Estevez A, et al. Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection. Biomed Mater. 2010;5(5): 055008.

  85. Pagonis TC, Chen J, Fontana CR, et al. Nanoparticle-based endodontic antimicrobial photodynamic therapy. J Endod. 2010;36(2):322–8.

    Article  PubMed  Google Scholar 

  86. Kishen A, Shi Z, Shrestha A, et al. An investigation on the antibacterial and antibiofilm efficacy of cationic nanoparticulates for root canal disinfection. J Endod. 2008;34(12):1515–20.

    Article  PubMed  Google Scholar 

  87. Mohammadi Z, Shalavi S. Antifungal effects of root canal irrigants and medicaments. An update review. N Y State Dent J. 2014;80(5): 58–63.

  88. de Souza-Filho FJ, Soares Ade J, Vianna ME, et al. Antimicrobial effect and pH of chlorhexidine gel and calcium hydroxide alone and associated with other materials. Braz Dent J. 2008;19(1):28–33.

    Article  PubMed  Google Scholar 

  89. Gomes BP, Montagner F, Berber VB, et al. Antimicrobial action of intracanal medicaments on the external root surface. J Dent. 2009;37(1):76–81.

    Article  CAS  PubMed  Google Scholar 

  90. Schafer E, Bossmann K. Antimicrobial efficacy of chlorhexidine and two calcium hydroxide formulations against Enterococcus faecalis. J Endod. 2005;31(1):53–6.

    Article  PubMed  Google Scholar 

  91. Huang J, Wong HL, Zhou Y, et al. In vitro studies and modeling of a controlled-release device for root canal therapy. J Control Release. 2000;67(2–3):293–307.

    Article  CAS  PubMed  Google Scholar 

  92. Lee DY, Spangberg LS, Bok YB, et al. The sustaining effect of three polymers on the release of chlorhexidine from a controlled release drug device for root canal disinfection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(1):105–11.

    Article  PubMed  Google Scholar 

  93. Duarte MA, Ordinola-Zapata R, Bernardes RA, et al. Influence of calcium hydroxide association on the physical properties of AH Plus. J Endod. 2010;36(6):1048–51.

    Article  PubMed  Google Scholar 

  94. Bailon-Sanchez ME, Baca P, Ruiz-Linares M, et al. Antibacterial and anti-biofilm activity of AH plus with chlorhexidine and cetrimide. J Endod. 2014;40(7):977–81.

    Article  PubMed  Google Scholar 

  95. Ruiz-Linares M, Bailon-Sanchez ME, Baca P, et al. Physical properties of AH Plus with chlorhexidine and cetrimide. J Endod. 2013;39(12):1611–4.

    Article  PubMed  Google Scholar 

  96. Arias-Moliz MT, Ruiz-Linares M, Cassar G, et al. The effect of benzalkonium chloride additions to AH Plus sealer. Antimicrobial, physical and chemical properties. J Dent. 2015; 43(7):846–54.

  97. Bansal R, Bansal R. Regenerative endodontics: a state of the art. Indian J Dent Res. 2011;22(1):122–31.

    Article  PubMed  Google Scholar 

  98. Strom TA, Arora A, Osborn B, et al. Endodontic release system for apexification with calcium hydroxide microspheres. J Dent Res. 2012;91(11):1055–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Hoshino E, Kurihara-Ando N, Sato I, et al. In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int Endod J. 1996;29(2):125–30.

    Article  CAS  PubMed  Google Scholar 

  100. Albuquerque MT, Valera MC, Nakashima M, et al. Tissue-engineering-based strategies for regenerative endodontics. J Dent Res. 2014;93(12):1222–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sato I, Ando-Kurihara N, Kota K, et al. Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. Int Endod J. 1996;29(2):118–24.

    Article  CAS  PubMed  Google Scholar 

  102. Montero-Miralles P, Martin-Gonzalez J, Alonso-Ezpeleta O, et al. Effectiveness and clinical implications of the use of topical antibiotics in regenerative endodontic procedures: a review. Int Endod J. 2018;51(9):981–8.

    Article  CAS  PubMed  Google Scholar 

  103. Bottino MC, Arthur RA, Waeiss RA, et al. Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria. Clin Oral Investig. 2014;18(9):2151–8.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Palasuk J, Kamocki K, Hippenmeyer L, et al. Bimix antimicrobial scaffolds for regenerative endodontics. J Endod. 2014;40(11):1879–84.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Minami H, Suzuki S, Minesaki Y, et al. In vitro evaluation of the influence of repairing condition of denture base resin on the bonding of autopolymerizing resins. J Prosthet Dent. 2004;91(2):164–70.

    Article  CAS  PubMed  Google Scholar 

  106. Harwood CL. The evidence base for current practices in prosthodontics. Eur J Prosthodont Restor Dent. 2008;16(1):24–34.

    PubMed  Google Scholar 

  107. Bowen Antolin A, Pascua Garcia MT, Nasimi A. Infections in implantology: from prophylaxis to treatment. Med Oral Patol Oral Cir Bucal. 2007;12(4):e323–30.

    PubMed  Google Scholar 

  108. Khatoon Z, McTiernan CD, Suuronen EJ, et al. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon. 2018;4(12):e01067-01067.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Abtahi J, Agholme F, Sandberg O, et al. Effect of local vs. systemic bisphosphonate delivery on dental implant fixation in a model of osteonecrosis of the jaw. J Dent Res. 2013;92(3): 279–83.

  110. Parnia F, Yazdani J, Javaherzadeh V, et al. Overview of nanoparticle coating of dental implants for enhanced osseointegration and antimicrobial purposes. J Pharm Pharm Sci. 2017;20:148–60.

    Article  CAS  PubMed  Google Scholar 

  111. Kazek-Kesik A, Nosol A, Plonka J, et al. PLGA-amoxicillin-loaded layer formed on anodized Ti alloy as a hybrid material for dental implant applications. Mater Sci Eng C Mater Biol Appl. 2019;94:998–1008.

    Article  CAS  PubMed  Google Scholar 

  112. Martin V, Bettencourt A, et al. Bone regeneration: biomaterials as local delivery systems with improved osteoinductive properties. Mater Sci Eng C Mater Biol Appl. 2018;82:363–71.

    Article  CAS  PubMed  Google Scholar 

  113. Chai F, Hornez JC, Blanchemain N, et al. Antibacterial activation of hydroxyapatite (HA) with controlled porosity by different antibiotics. Biomol Eng. 2007;24(5):510–4.

    Article  CAS  PubMed  Google Scholar 

  114. Gupta AK, Kumar P, Keshav K, et al. Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone. Indian J Orthop. 2015;49(6):649–55.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Santana RB, de Mattos CM, Van Dyke T. Efficacy of combined regenerative treatments in human mandibular class II furcation defects. J Periodontol. 2009;80(11):1756–64.

    Article  PubMed  Google Scholar 

  116. de Souza CA, Colombo AP, Souto RM, et al. Adsorption of chlorhexidine on synthetic hydroxyapatite and in vitro biological activity. Colloids Surf B Biointerfaces. 2011;87(2):310–8.

    Article  CAS  PubMed  Google Scholar 

  117. Rolla G, Loe H, Schiott CR. The affinity of chlorhexidine for hydroxyapatite and salivary mucins. J Periodontal Res. 1970;5(2):90–5.

    Article  CAS  PubMed  Google Scholar 

  118. Emilson CG, Ericson T, Heyden G, et al. Uptake of chlorhexidine to hydroxyapatite. J Periodontal Res Suppl. 1973;12:17–21.

    Article  CAS  PubMed  Google Scholar 

  119. Jennings KJ, Samaranayake LP. The persistence of microorganisms on impression materials following disinfection. Int J Prosthodont. 1991;4(4):382–7.

    CAS  PubMed  Google Scholar 

  120. Flanagan DA, Palenik CJ, Setcos JC, et al. Antimicrobial activities of dental impression materials. Dent Mater. 1998;14(6):399–404.

    Article  CAS  PubMed  Google Scholar 

  121. Oehring H, Welker D, Wolf D, et al. Microbiological studies of self-disinfecting alginate impression materials. Dtsch Zahn Mund Kieferheilkd Zentralbl. 1992;80(3):165–70.

    CAS  PubMed  Google Scholar 

  122. Moreira ACA, Wanderley-Cruz JF. Efetividade da clorexidina incorporada a hidrocolóide irreversível. Rev Cienc Med Biol. 2005;4(2):113–7.

    Google Scholar 

  123. Gendreau L, Loewy ZG. Epidemiology and etiology of denture stomatitis. J Prosthodont. 2011;20(4):251–60.

    Article  PubMed  Google Scholar 

  124. Redding S, Bhatt B, Rawls HR, et al. Inhibition of Candida albicans biofilm formation on denture material. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(5):669–72.

    Article  PubMed  Google Scholar 

  125. Pusateri CR, Monaco EA, Edgerton M. Sensitivity of Candida albicans biofilm cells grown on denture acrylic to antifungal proteins and chlorhexidine. Arch Oral Biol. 2009;54(6):588–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ellepola AN, Joseph BK, Altarakemah Y, et al. In vitro adhesion of oral Candida dubliniensis isolates to acrylic denture surfaces following brief exposure to sub-cidal concentrations of polyenes, azoles and chlorhexidine. Med Princ Pract. 2015;24(1):58–64.

    Article  PubMed  Google Scholar 

  127. McCourtie J, MacFarlane TW, Samaranayake LP. A comparison of the effects of chlorhexidine gluconate, amphotericin B and nystatin on the adherence of Candida species to denture acrylic. J Antimicrob Chemother. 1986;17(5):575–83.

    Article  CAS  PubMed  Google Scholar 

  128. Cartagena AF, Esmerino LA, Polak-Junior R, et al. New denture adhesive containing miconazole nitrate polymeric microparticles: Antifungal, adhesive force and toxicity properties. Dent Mater. 2017;33(2):e53-61.

    Article  CAS  PubMed  Google Scholar 

  129. Amin WM, Al-Ali MH, Salim NA, et al. A new form of intraoral delivery of antifungal drugs for the treatment of denture-induced oral candidosis. Eur J Dent. 2009;3(4):257–66.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Cao Z, Sun X, Yeh CK, et al. Rechargeable infection-responsive antifungal denture materials. J Dent Res. 2010;89(12):1517–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Darwish RM, Amin WM, Al-Ali MH, et al. Study of the elution of fluconazole from a self-polymerizing acrylic resin and its activity against resistant Candida albicans. J Mater Sci Mater Med. 2011;22(8):1885–90.

    Article  CAS  PubMed  Google Scholar 

  132. Ryalat S, Darwish R, Amin W. New form of administering chlorhexidine for treatment of denture-induced stomatitis. Ther Clin Risk Manag. 2011;7:219–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Salim N, Satterthwaite J, Rautemaa R, et al. Impregnation with antimicrobials has an impact on degree of conversion and colour stability of acrylic liner. Dent Mater J. 2012;31(6):1008–13.

    Article  CAS  PubMed  Google Scholar 

  134. Rijo I, Pedro D, Costa J, et al. Chlorhexidine loading of acrylic reline resins – Microhardness and flexural strength after thermal aging. Rev Port Estomatol Cir Maxilofac. 2018;59(3):154–61.

    Google Scholar 

  135. Truhlar MR, Shay K, Sohnle P. Use of a new assay technique for quantification of antifungal activity of nystatin incorporated in denture liners. J Prosthet Dent. 1994;71(5):517–24.

    Article  CAS  PubMed  Google Scholar 

  136. Radnai M, Whiley R, Friel T, et al. Effect of antifungal gels incorporated into a tissue conditioning material on the growth of Candida albicans. Gerodontology. 2010;27(4):292–6.

    Article  PubMed  Google Scholar 

  137. Sharma S, Hegde V. Comparative evaluation of antifungal activity of melaleuca oil and fluconazole when incorporated in tissue conditioner: an in vitro study. J Prosthodont. 2014;23(5):367–73.

    Article  PubMed  Google Scholar 

  138. Thomas CJ, Nutt GM. The in vitro fungicidal properties of Visco-gel, alone and combined with nystatin and amphotericin B. J Oral Rehabil. 1978;5(2):167–72.

    Article  CAS  PubMed  Google Scholar 

  139. Salim N, Satterthwaite JD, Rautemaa R, et al. Impregnation with antimicrobials challenge bonding properties and water sorption behaviour of an acrylic liner. J Dent. 2012;40(8):693–9.

    Article  CAS  PubMed  Google Scholar 

  140. Salim N, Moore C, Silikas N, et al. Chlorhexidine is a highly effective topical broad-spectrum agent against Candida spp. Int J Antimicrob Agents. 2013;41(1):65–9.

    Article  CAS  PubMed  Google Scholar 

  141. Salim N, Moore C, Silikas N, et al. Candidacidal effect of fluconazole and chlorhexidine released from acrylic polymer. J Antimicrob Chemother. 2013;68(3):587–92.

    Article  CAS  PubMed  Google Scholar 

  142. de Castro DT, Valente ML, Agnelli JA, et al. In vitro study of the antibacterial properties and impact strength of dental acrylic resins modified with a nanomaterial. J Prosthet Dent. 2016;115(2):238–46.

    Article  CAS  PubMed  Google Scholar 

  143. Li Z, Sun J, Lan J, et al. Effect of a denture base acrylic resin containing silver nanoparticles on Candida albicans adhesion and biofilm formation. Gerodontology. 2016;33(2):209–16.

    Article  CAS  PubMed  Google Scholar 

  144. Yoshida K, Atsuta M. Properties of fluoride-releasing light-activated resin cement. Dent Mater. 1999;15(5):337–41.

    Article  CAS  PubMed  Google Scholar 

  145. Wilson AD, Groffman DM, Kuhn AT. The release of fluoride and other chemical species from a glass-ionomer cement. Biomaterials. 1985;6(6):431–3.

    Article  CAS  PubMed  Google Scholar 

  146. Forsten L. Short- and long-term fluoride release from glass ionomers and other fluoride-containing filling materials in vitro. Scand J Dent Res. 1990;98(2):179–85.

    CAS  PubMed  Google Scholar 

  147. Herrera M, Carrion P, Baca P, et al. In vitro antibacterial activity of glass-ionomer cements. Microbios. 2001;104(409):141–8.

    CAS  PubMed  Google Scholar 

  148. Duque C, Negrini Tde C, Hebling J, et al. Inhibitory activity of glass-ionomer cements on cariogenic bacteria. Oper Dent. 2005;30(5):636–40.

    PubMed  Google Scholar 

  149. Kim HJ, Son JS, Kim KH, et al. Antimicrobial Activity of Glass lonomer Cement Incorporated with Chlorhexidine-Loaded Zeolite Nanoparticles. J Nanosci Nanotechnol. 2016;16(2):1450–3.

    Article  CAS  PubMed  Google Scholar 

  150. Oguz Ahmet S, Mutluay MM, Seyfioglu Polat Z, et al. Addition of benzalkonium chloride to self-adhesive resin-cements: some clinically relevant properties. Acta Odontol Scand. 2014;72(8):831–8.

    Article  CAS  PubMed  Google Scholar 

  151. Lovrov S, Hertrich K, Hirschfelder U. Enamel Demineralization during Fixed Orthodontic Treatment - Incidence and Correlation to Various Oral-hygiene Parameters. J Orofac Orthop. 2007;68(5):353–63.

    Article  PubMed  Google Scholar 

  152. Bourbia M, Ma D, Cvitkovitch DG, et al. Cariogenic bacteria degrade dental resin composites and adhesives. J Dent Res. 2013;92(11):989–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Nelson-Filho P, Carpio-Horta KO, Andrucioli MC, et al. Molecular detection of Aggregatibacter actinomycetemcomitans on metallic brackets by the checkerboard DNA-DNA hybridization technique. Am J Orthod Dentofacial Orthop. 2012;142(4):481–6.

    Article  PubMed  Google Scholar 

  154. Slutzky H, Feuerstein O, Namuz K, et al. The effects of in vitro fluoride mouth rinse on the antibacterial properties of orthodontic cements. Orthod Craniofac Res. 2014;17(3):150–7.

    Article  CAS  PubMed  Google Scholar 

  155. Singh C, Dua V, Vyas M, et al. Evaluation of the antimicrobial and physical properties of an orthodontic photo-activated adhesive modified with an antiplaque agent: an in vitro study. Indian J Dent Res. 2013;24(6):694–700.

    Article  PubMed  Google Scholar 

  156. Farret MM, de Lima EM, Mota EG, et al. Can we add chlorhexidine into glass ionomer cements for band cementation? Angle Orthod. 2011;81(3):496–502.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Degrazia FW, Leitune VC, Garcia IM, et al. Effect of silver nanoparticles on the physicochemical and antimicrobial properties of an orthodontic adhesive. J Appl Oral Sci. 2016;24(4):404–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Altmann AS, Collares FM, Ogliari FA, et al. Effect of methacrylated-based antibacterial monomer on orthodontic adhesive system properties. Am J Orthod Dentofacial Orthop. 2015;147(4 Suppl):S82–7.

    Article  PubMed  Google Scholar 

  159. Fatani EJ, Almutairi HH, Alharbi AO, et al. In vitro assessment of stainless steel orthodontic brackets coated with titanium oxide mixed Ag for anti-adherent and antibacterial properties against Streptococcus mutans and Porphyromonas gingivalis. Microb Pathog. 2017;112:190–4.

    Article  CAS  PubMed  Google Scholar 

  160. Ghasemi T, Arash V. Antimicrobial effect, frictional resistance, and surface roughness of stainless steel orthodontic brackets coated with nanofilms of silver and titanium oxide: a preliminary study. Microsc Res Tech. 2017;80(6):599–607.

    Article  CAS  PubMed  Google Scholar 

  161. Arash V, Keikhaee F, Rabiee SM, et al. Evaluation of Antibacterial Effects of Silver-Coated Stainless Steel Orthodontic Brackets. J Dent (Tehran). 2016;13(1):49–54.

    Google Scholar 

  162. Ryu HS, Bae IH, Lee KG, et al. Antibacterial effect of silver-platinum coating for orthodontic appliances. Angle Orthod. 2012;82(1):151–7.

    Article  PubMed  Google Scholar 

  163. Ramazanzadeh B, Jahanbin A, Yaghoubi M, et al. Comparison of antibacterial effects of ZnO and CuO nanoparticles coated brackets against Streptococcus mutans. J Dent (Shiraz). 2015;16(3):200–5.

    Google Scholar 

  164. Chambers C, Stewart S, Su B, et al. Prevention and treatment of demineralisation during fixed appliance therapy: a review of current methods and future applications. Br Dent J. 2013;215(10):505–11.

    Article  CAS  PubMed  Google Scholar 

  165. Liu Y, Zhang L, Niu LN, et al. Antibacterial and remineralizing orthodontic adhesive containing quaternary ammonium resin monomer and amorphous calcium phosphate nanoparticles. J Dent. 2018;72:53–63.

    Article  CAS  PubMed  Google Scholar 

  166. Degrazia FW, Genari B, Leitune VCB, et al. Polymerisation, antibacterial and bioactivity properties of experimental orthodontic adhesives containing triclosan-loaded halloysite nanotubes. J Dent. 2018;69:77–82.

    Article  CAS  PubMed  Google Scholar 

  167. Freitas M, Nunes LV, Comar LP, et al. In vitro effect of a resin infiltrant on different artificial caries-like enamel lesions. Arch Oral Biol. 2018;95:118–24.

    Article  CAS  PubMed  Google Scholar 

  168. Kielbassa AM, Ulrich I, Werth VD, et al. External and internal resin infiltration of natural proximal subsurface caries lesions: a valuable enhancement of the internal tunnel restoration. Quintessence Int. 2017;48(5):357–68.

    PubMed  Google Scholar 

  169. Schneider H, Park KJ, Rueger C, et al. Imaging resin infiltration into non-cavitated carious lesions by optical coherence tomography. J Dent. 2017;60:94–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Fundação para a Ciência e Tecnologia (FCT) for the financial support under the projects UIDB/04138/2020 and UIDP/04138/2020 (iMed.ULisboa).

Funding

This work was funded by Fundação para a Ciência e a Tecnologia (FCT), Portugal (UIDB/04138/2020 and UIDP/04138/2020).

Author information

Authors and Affiliations

  1. Unidade de Investigação em Ciências Orais e Biomédicas (UICOB), Faculdade de Medicina Dentária, Universidade de Lisboa, Rua Professora Teresa Ambrósio, 1600-277, Lisboa, Portugal

    Joana Vieira Costa, Jaime Portugal & Cristina Bettencourt Neves

  2. Research Institute for Medicines (iMED.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Rua Professor Gama Pinto, 1649-003, Lisboa, Portugal

    Ana F. Bettencourt

Authors
  1. Joana Vieira Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jaime Portugal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Bettencourt Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana F. Bettencourt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Joana Costa: writing—original draft; Jaime Portugal: writing—review and editing; supervision; Cristina Neves: conceptualization; writing—review and editing; supervision; Ana Bettencourt: conceptualization; writing—review and editing; supervision; funding acquisition.

Corresponding authors

Correspondence to Cristina Bettencourt Neves or Ana F. Bettencourt.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors agreed with the content of this manuscript, and all gave explicit consent to submit it for publication.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa, J.V., Portugal, J., Neves, C. . et al. Should local drug delivery systems be used in dentistry?. Drug Deliv. and Transl. Res. 12, 1395–1407 (2022). https://doi.org/10.1007/s13346-021-01053-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-021-01053-x

Keywords

Search

Navigation