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Local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing in periodontitis: Randomized, placebo-controlled, double-blind split-mouth clinical trial

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Abstract

Objective

Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT).

Materials and methods

Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 μg of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1α, IL-6, TNFα, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy.

Results

PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15.

Conclusion

We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT.

Clinical relevance

Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy.

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References

  1. Aggarwal BB, Yuan W, Li S, Gupta SC (2013) Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res 57:1529–1542

    PubMed  Google Scholar 

  2. Akram Z, Abduljabbar T, Kellesarian SV, Abu Hassan MI, Javed F, Vohra F (2017) Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in the management of periodontal disease: a systematic review. Br J Clin Pharmacol 83:444–454

    PubMed  Google Scholar 

  3. Amalraj A, Varma K, Jacob J, Divya C, Kunnumakkara AB, Stohs SJ, Gopi S (2017) A novel highly bioavailable curcumin formulation improves symptoms and diagnostic indicators in rheumatoid arthritis patients: a randomized, double-blind, placebo-controlled, two-dose, three-arm, and parallel-group study. J Med Food 20:1022–1030

    PubMed  Google Scholar 

  4. Anitha V, Rajesh P, Shanmugam M, Priya BM, Prabhu S, Shivakumar V (2015) Comparative evaluation of natural curcumin and synthetic chlorhexidine in the management of chronic periodontitis as a local drug delivery: a clinical and microbiological study. Indian J Dent Res 26:53–56

    PubMed  Google Scholar 

  5. Anuradha BR, Bai YD, Sailaja S, Sudhakar J, Priyanka M, Deepika V (2015) Evaluation of anti-inflammatory effects of curcumin gel as an adjunct to scaling and root planing: a clinical study. J Int Oral Health 7:90–93

    PubMed  PubMed Central  Google Scholar 

  6. Asteriou E, Gkoutzourelas A, Mavropoulos A, Katsiari C, Sakkas L, Bogdanos D (2018) Curcumin for the management of periodontitis and early ACPA-positive rheumatoid arthritis: killing two birds with one stone. Nutrients 10

  7. Behal R, Mali AM, Gilda SS et al (2011) Evaluation of local drug-delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: a clinical and microbiological study. J Indian Soc Periodontol 15:35–38

    PubMed  PubMed Central  Google Scholar 

  8. Bhatia M, Urolagin SS, Pentyala KB, Urolagin SB, K BM, Bhoi S (2014) Novel therapeutic approach for the treatment of periodontitis by curcumin. J Clin Diagn Res 8:ZC65–ZC69

    PubMed  PubMed Central  Google Scholar 

  9. Correa MG, Pires PR, Ribeiro FV et al (2017) Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. J Periodontal Res 52:201–209

    PubMed  Google Scholar 

  10. Curylofo-Zotti FA, Elburki MS, Oliveira PA, Cerri PS, Santos LA, Lee HM, Johnson F, Golub LM, Rossa Junior C, Guimarães-Stabili MR (2018) Differential effects of natural curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis. Arch Oral Biol 91:42–50

    PubMed  Google Scholar 

  11. De Almeida Brandao D, Spolidorio LC, Johnson F et al (2019) Dose-response assessment of chemically modified curcumin in experimental periodontitis. J Periodontol 90:535–545

    PubMed  Google Scholar 

  12. Elavarasu S, Suthanthiran T, Thangavelu A, Alex S, Palanisamy VK, Kumar TS (2016) Evaluation of superoxide dismutase levels in local drug delivery system containing 0.2% curcumin strip as an adjunct to scaling and root planing in chronic periodontitis: a clinical and biochemical study. J Pharm Bioallied Sci 8:S48–S52

    PubMed  PubMed Central  Google Scholar 

  13. Elburki MS, Rossa C, Guimaraes MR et al (2014) A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations. Mediators Inflamm 2014:959471

    PubMed  PubMed Central  Google Scholar 

  14. Epstein J, Docena G, Macdonald TT et al (2010) Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr 103:824–832

    PubMed  Google Scholar 

  15. Golub LM, Elburki MS, Walker C, Ryan M, Sorsa T, Tenenbaum H, Goldberg M, Wolff M, Gu Y (2016) Non-antibacterial tetracycline formulations: host-modulators in the treatment of periodontitis and relevant systemic diseases. Int Dent J 66:127–135

    PubMed  Google Scholar 

  16. Gottumukkala SN, Koneru S, Mannem S et al (2013) Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on clinical and microbiological parameters in chronic periodontitis patients: a pilot randomized clinical trial. Contemp Clin Dent 4:186–191

    PubMed  PubMed Central  Google Scholar 

  17. Guimaraes MR, Coimbra LS, De Aquino SG et al (2011) Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J Periodontal Res 46:269–279

    PubMed  PubMed Central  Google Scholar 

  18. Guimaraes MR, De Aquino SG, Coimbra LS et al (2012) Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun 18:155–163

    PubMed  Google Scholar 

  19. Guimaraes-Stabili MR, De Aquino SG, De Almeida Curylofo F et al (2019) Systemic administration of curcumin or piperine enhances the periodontal repair: a preliminary study in rats. Clin Oral Investig 23:3297–3306

    PubMed  Google Scholar 

  20. Gupta SC, Patchva S, Koh W, Aggarwal BB (2012) Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 39:283–299

    PubMed  PubMed Central  Google Scholar 

  21. Hanai H, Sugimoto K (2009) Curcumin has bright prospects for the treatment of inflammatory bowel disease. Curr Pharm Des 15:2087–2094

    PubMed  Google Scholar 

  22. Hayakawa H, Minaniya Y, Ito K, Yamamoto Y, Fukuda T (2011) Difference of curcumin content in Curcuma longa L. (Zingiberaceae) caused by hybridization with other curcuma species. American Journal of Plant Sciences 02:111–119

    Google Scholar 

  23. Heitz-Mayfield LJ, Trombelli L, Heitz F et al (2002) A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol 29(Suppl 3):92–102 discussion 160-102

    PubMed  Google Scholar 

  24. Hugar SS, Patil S, Metgud R, Nanjwade B, Hugar SM (2016) Influence of application of chlorhexidine gel and curcumin gel as an adjunct to scaling and root planing: a interventional study. J Nat Sci Biol Med 7:149–154

    PubMed  PubMed Central  Google Scholar 

  25. Ikram S, Hassan N, Raffat MA, Mirza S, Akram Z (2018) Systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials using probiotics in chronic periodontitis. J Investig Clin Dent 9:e12338

    PubMed  Google Scholar 

  26. Izui S, Sekine S, Maeda K, Kuboniwa M, Takada A, Amano A, Nagata H (2016) Antibacterial activity of curcumin against periodontopathic bacteria. J Periodontol 87:83–90

    PubMed  Google Scholar 

  27. Jalaluddin M, Jayanti I, Gowdar IM, Roshan R, Varkey RR, Thirutheri A (2019) Antimicrobial activity of Curcuma longa L. extract on periodontal pathogens. J Pharm Bioallied Sci 11:S203–S207

    PubMed  PubMed Central  Google Scholar 

  28. Jaswal R, Dhawan S, Grover V, Malhotra R (2014) Comparative evaluation of single application of 2% whole turmeric gel versus 1% chlorhexidine gel in chronic periodontitis patients: A pilot study. J Indian Soc Periodontol 18:575–580

    PubMed  PubMed Central  Google Scholar 

  29. John MT, Michalowicz BS, Kotsakis GA, Chu H (2017) Network meta-analysis of studies included in the Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis. J Clin Periodontol 44:603–611

    PubMed  PubMed Central  Google Scholar 

  30. Kassebaum NJ, Bernabe E, Dahiya M et al (2014) Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res 93:1045–1053

    PubMed  PubMed Central  Google Scholar 

  31. Kaur S, Sharma R, Sarangal V, Kaur N, Prashar P (2017) Evaluation of anti-inflammatory effects of systemically administered curcumin, lycopene and piperine as an adjunct to scaling and root planing: A clinical study. Ayu 38:117–121

    PubMed  PubMed Central  Google Scholar 

  32. Kaur H, Grover V, Malhotra R, Gupta M (2019) Evaluation of curcumin gel as adjunct to scaling & root planing in management of periodontitis- randomized clinical & biochemical investigation. Infect Disord Drug Targets 19:171–178

    PubMed  Google Scholar 

  33. Kinane DF, Demuth DR, Gorr SU et al (2007) Human variability in innate immunity. Periodontol 2000(45):14–34

    Google Scholar 

  34. Kudva P, Tabasum ST, Gupta S (2012) Comparative evaluation of the efficacy of turmeric and curcumin as a local drug delivery system: a clinicomicrobiological study. Gen Dent 60:e283–e287

    PubMed  Google Scholar 

  35. Kuriakose MA, Ramdas K, Dey B, Iyer S, Rajan G, Elango KK, Suresh A, Ravindran D, Kumar RR, R P, Ramachandran S, Kumar NA, Thomas G, Somanathan T, Ravindran HK, Ranganathan K, Katakam SB, Parashuram S, Jayaprakash V, Pillai MR (2016) A randomized double-blind placebo-controlled phase IIB trial of curcumin in oral leukoplakia. Cancer Prev Res (Phila) 9:683–691

    Google Scholar 

  36. Ma L, Zhang X, Ma Z, Shi H, Zhang Y, Wu M, Cui W (2018) Clinical effectiveness of Er: YAG lasers adjunct to scaling and root planing in non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled trials. Med Sci Monit 24:7090–7099

    PubMed  PubMed Central  Google Scholar 

  37. Manresa C, Sanz-Miralles EC, Twigg J et al (2018) Supportive periodontal therapy (SPT) for maintaining the dentition in adults treated for periodontitis. Cochrane Database Syst Rev 1:CD009376

    PubMed  Google Scholar 

  38. Martins SHL, Novaes AB Jr, Taba M Jr, Palioto DB, Messora MR, Reino DM, Souza SLS (2017) Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: a randomized controlled clinical trial. J Clin Periodontol 44:717–728

    PubMed  Google Scholar 

  39. Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili SA, Johnston TP, Abdollahi E, Sahebkar A (2018) Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev 17:125–135

    PubMed  Google Scholar 

  40. Nagasri M, Madhulatha M, Musalaiah SV, Kumar PA, Krishna CH, Kumar PM (2015) Efficacy of curcumin as an adjunct to scaling and root planning in chronic periodontitis patients: a clinical and microbiological study. J Pharm Bioallied Sci 7:S554–S558

    PubMed  PubMed Central  Google Scholar 

  41. Najafi S, Khayamzadeh M, Paknejad M, Poursepanj G, Kharazi Fard MJ, Bahador A (2016) An in vitro comparison of antimicrobial effects of curcumin-based photodynamic therapy and chlorhexidine, on aggregatibacter actinomycetemcomitans. J Lasers Med Sci 7:21–25

    PubMed  PubMed Central  Google Scholar 

  42. Nasra MM, Khiri HM, Hazzah HA et al (2017) Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis. Drug Deliv 24:133–142

    PubMed  Google Scholar 

  43. Panahi Y, Khalili N, Sahebi E, Namazi S, Reiner Ž, Majeed M, Sahebkar A (2017) Curcuminoids modify lipid profile in type 2 diabetes mellitus: a randomized controlled trial. Complement Ther Med 33:1–5

    PubMed  Google Scholar 

  44. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol 89(Suppl 1):S173–S182

    PubMed  Google Scholar 

  45. Peng S, Li Z, Zou L, Liu W, Liu C, McClements D (2018) Improving curcumin solubility and bioavailability by encapsulation in saponin-coated curcumin nanoparticles prepared using a simple pH-driven loading method. Food Funct 9:1829–1839

    PubMed  Google Scholar 

  46. Pourhajibagher M, Chiniforush N, Monzavi A, Barikani H, Monzavi MM, Sobhani S, Shahabi S, Bahador A (2018) Inhibitory effects of antimicrobial photodynamic therapy with curcumin on biofilm-associated gene expression profile of Aggregatibacter actinomycetemcomitans. J Dent (Tehran) 15:169–177

    Google Scholar 

  47. Preshaw PM (2018) Host modulation therapy with anti-inflammatory agents. Periodontol 2000(76):131–149

    Google Scholar 

  48. Raghava KV, Sistla KP, Narayan SJ, Yadalam U, Bose A, Mitra K (2019) Efficacy of curcumin as an adjunct to scaling and root planing in chronic periodontitis patients: a randomized controlled clinical trial. J Contemp Dent Pract 20:842–846

    PubMed  Google Scholar 

  49. Ravishankar PL, Kumar YP, Anila EN, Chakraborty P, Malakar M, Mahalakshmi R (2017) Effect of local application of curcumin and ornidazole gel in chronic periodontitis patients. Int J Pharm Investig 7:188–192

    PubMed  PubMed Central  Google Scholar 

  50. Ren C, Mcgrath C, Jin L et al (2017) The effectiveness of low-level laser therapy as an adjunct to non-surgical periodontal treatment: a meta-analysis. J Periodontal Res 52:8–20

    PubMed  Google Scholar 

  51. Ricci Donato HA, Pratavieira S, Grecco C, Brugnera-Júnior A, Bagnato VS, Kurachi C (2017) Clinical comparison of two photosensitizers for oral cavity decontamination. Photomed Laser Surg 35:105–110

    PubMed  Google Scholar 

  52. Roberts FA, Darveau RP (2002) Beneficial bacteria of the periodontium. Periodontol 2000 30:40–50

    PubMed  Google Scholar 

  53. Sandeep IS, Das S, Nasim N, Mishra A, Acharya L, Joshi RK, Nayak S, Mohanty S (2017) Differential expression of CURS gene during various growth stages, climatic condition and soil nutrients in turmeric (Curcuma longa): Towards site specific cultivation for high curcumin yield. Plant Physiol Biochem 118:348–355

    PubMed  Google Scholar 

  54. Shahzad M, Millhouse E, Culshaw S, Edwards CA, Ramage G, Combet E (2015) Selected dietary (poly)phenols inhibit periodontal pathogen growth and biofilm formation. Food Funct 6:719–729

    PubMed  Google Scholar 

  55. Sharma RA, Mclelland HR, Hill KA et al (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7:1894–1900

    PubMed  Google Scholar 

  56. Shinwari MS, Tanwir F, Hyder PR, Bin Saeed MH (2014) Host modulation therapeutics in periodontics: role as an adjunctive periodontal therapy. J Coll Physicians Surg Pak 24:676–684

    PubMed  Google Scholar 

  57. Singh A, Sridhar R, Shrihatti R, Mandloy A (2018) Evaluation of turmeric chip compared with chlorhexidine chip as a local drug delivery agent in the treatment of chronic periodontitis: a split mouth randomized controlled clinical trial. J Altern Complement Med 24:76–84

    PubMed  Google Scholar 

  58. Slots J (2017) Periodontitis: facts, fallacies and the future. Periodontol 2000(75):7–23

    Google Scholar 

  59. Socransky SS, Smith C, Martin L, Paster BJ, Dewhirst FE, Levin AE (1994) “Checkerboard” DNA-DNA hybridization. Biotechniques 17:788–792

    PubMed  Google Scholar 

  60. Sreedhar A, Sarkar I, Rajan P, Pai J, Malagi S, Kamath V, Barmappa R (2015) Comparative evaluation of the efficacy of curcumin gel with and without photo activation as an adjunct to scaling and root planing in the treatment of chronic periodontitis: a split mouth clinical and microbiological study. J Nat Sci Biol Med 6:S102–S109

    PubMed  PubMed Central  Google Scholar 

  61. Xiao CJ, Yu XJ, Xie JL, Liu S, Li S (2018) Protective effect and related mechanisms of curcumin in rat experimental periodontitis. Head Face Med 14:12

    PubMed  PubMed Central  Google Scholar 

  62. Zambrano LMG, Brandao DA, Rocha FRG, Marsiglio RP, Longo IB, Primo FL, Tedesco AC, Guimaraes-Stabili MR, Rossa Junior C (2018) Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease. Sci Rep 8:6652

    PubMed  PubMed Central  Google Scholar 

  63. Zandbergen D, Slot DE, Cobb CM, van der Weijden FA (2013) The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol 84:332–351

    PubMed  Google Scholar 

  64. Zhou T, Chen D, Li Q, Sun X, Song Y, Wang C (2013) Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats. Acta Odontol Scand 71:349–356

    PubMed  Google Scholar 

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Acknowledgments

The authors are thankful to Izilvânia M. Q. Barreto from Guarulhos University for the technical support with the DNA-DNA checkerboard hybridization technique.

Funding

This study was financially supported by Brazilian National Council for Scientific and Technological Development (CNPq 440588/2014-6) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

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Correspondence to Carlos Rossa Jr.

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Pérez-Pacheco, C., Fernandes, N., Primo, F. et al. Local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing in periodontitis: Randomized, placebo-controlled, double-blind split-mouth clinical trial. Clin Oral Invest 25, 3217–3227 (2021). https://doi.org/10.1007/s00784-020-03652-3

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