Nanoparticle-based oral rinses for plaque control: A systematic review of efficacy and safety

This systematic review analyzes clinical, preclinical, and patent literature on nano-enabled mouthwashes for plaque control. Searches were conducted across PubMed, Embase, Scopus, Web of Science, and three patent databases (Google Patents, Lens, and Espacenet) for English-language records published from January 2018 to June 2025. Eligible studies included randomized controlled trials (RCTs), other human investigations, and in vitro, ex vivo, or animal studies evaluating nanoparticle-based mouthrinses. Two reviewers independently extracted data, assessed bias risk using the RoB-2 tool, and rated evidence certainty with the GRADE approach. Findings were narratively summarized due to methodological differences. A total of 38 records met the inclusion criteria: 25 primary research studies (10 RCTs; 15 in vitro/animal) and 13 patents on nano-enabled mouthwashes. Silver nanoparticles were the most studied, followed by zinc oxide, titanium dioxide, calcium phosphate, and herbal nanoemulsions. Nano-enabled mouthwashes reduced plaque index by a pooled mean difference of 0.32(95 % CI: 0.25 to 0.39; I² = 45 %) and gingival index by a pooled mean difference of 0.27(95 % CI: 0.21 to 0.33; I² = 50 %) units, respectively, comparable to 0.12 % chlorhexidine (CHX), with fewer reports of staining or taste changes. Nanosilver rinses decreased white-spot lesions in orthodontic patients by 66 %, and titanium dioxide-based rinses halved dentine hypersensitivity scores. Preclinical studies showed ≥2-log reductions in biofilm viability, pH-triggered mineral release, and nanozyme-like catalytic activity. Thirteen patents (2003-2024) described stable nanoformulations, odour-neutralizing systems, mucoadhesive carriers, and theranostic technologies, indicating significant commercial interest. Evidence certainty was moderate for short-term plaque and gingival control but low for caries prevention and long-term safety. Nano-enabled mouthwashes show promise as alternatives to CHX, but large, long-term RCTs are needed to confirm efficacy, monitor safety, and support clinical use.