ORIGINAL ARTICLE 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 Cindy Grace Pérez-Pacheco 1 & Natalie Ap. Rodrigues Fernandes 1 & Fernando Lucas Primo 2 & Antonio Claudio Tedesco 3 & Emily Bellile 4 & Belen Retamal-Valdes 5 & Magda Feres 5 & Morgana Rodrigues Guimarães-Stabili 1 & Carlos Rossa Jr 1 Received: 18 June 2020 /Accepted: 20 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 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 nonsur- gical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy. Keywords Curcumin . Periodontitis . Dental Scaling . Nanoparticles Introduction Periodontitis is a chronic inflammatory condition by destruc- tion of tooth-supporting tissues [44]. Periodontitis was considered the 6th most prevalent chronic inflammatory con- dition worldwide in 2010 [30]. Disease is initiated by a dysbiosis between host and micro- organisms of the dental biofilm [33, 58]. The standard therapy * Carlos Rossa, Jr c.rossa@unesp.br 1 Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University (UNESP), Araraquara, SP, Brazil 2 Department of Bioprocess and Biotechnology, Faculty of Pharmaceutical Sciences of Araraquara, Sao Paulo State University (UNESP), Araraquara, SP, Brazil 3 Department of Chemistry, Center of Nanotechnology and Tissue Engineering- Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil 4 Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA 5 Department of Periodontology and Oral Implantology, Dental Research Division, Universidade de Guarulhos - UNG, Sao Paulo, SP, Brazil Clinical Oral Investigations https://doi.org/10.1007/s00784-020-03652-3