Repeated local dosing of Nowarta110 produced no detected treatment-related toxicity in mice over 12 weeks, the study reports. The assessment covered clinical observations, food intake and body weight, blood counts, serum chemistry, urine, organ weights, tissue examination and measurements of silver in plasma. The authors described the treatment as well tolerated across the routes tested.
Three routes, one formulation
Nowarta110 has a silver nanoparticle core with an organic fig-extract shell. The mice received it once daily for 12 consecutive weeks through the skin, the oral mucosa or by intravaginal dosing. The topical dose was 340 microlitres per day, the oral dose was 40 microlitres, and the intravaginal dose ranged from 7 to 10 microlitres per mouse per day.
The control, topical and oral groups each included 10 male and 10 female mice. The intravaginal group included 10 female mice, so that route did not provide a male comparison.
Most routine measures stayed steady
The researchers combined repeated in-life monitoring with blood tests, serum biochemistry, urinalysis, organ-weight measurements, histopathology and toxicokinetic profiling. Blood and serum chemistry results were compared with a pooled week 0 baseline using linear models and Benjamini-Hochberg adjustment. Organ weights were assessed with Welch tests and Holm adjustment.
Blood-cell measurements were largely stable across groups and time points. Female lymphocyte counts rose at 12 weeks after topical and oral administration, but the increase was not sustained, was not accompanied by broader leukocyte changes and did not follow a consistent dose or route pattern.
Serum biochemistry showed minimal changes. Alkaline phosphatase had modest decreases across all three routes, but there were no concurrent changes in other liver markers or coordinated changes in renal, electrolyte or metabolic measures. Urinalysis showed no differences by group, time, sex or route. Urine pH remained around 5, while protein, blood, leukocytes and infection markers were negative in all animals.
Food intake remained comparable with controls, averaging 141.1 grams per cage per week in males and 106.9 grams in females. Body weight increased steadily, with no sustained weight loss or suppressed expected gain.
Organ weights were broadly comparable between treated and control mice. The few statistically significant differences were sporadic and showed no consistent sex or route pattern, so the authors did not consider them treatment-related. Histopathology found no treatment-related lesions or neoplastic changes after topical, oral-mucosal or intravaginal dosing. Observed findings were considered incidental and comparably frequent in controls and treated mice; cardiac findings appeared across all groups, against a cited untreated-animal background range of 10% to 60%.
Plasma silver stayed below quantification
Separate toxicokinetic cohorts were used to look for systemic exposure. The intravaginal cohort included 18 female mice, while oral and topical testing used three males and three females at each sampling time. A validated ICP-MS assay measured total plasma silver as a surrogate of systemic exposure. All analyzed plasma samples were below the lower limit of quantification, 22.6 nanograms per millilitre, indicating no measurable systemic exposure in the assay.
A result with clear limits
That finding should be read narrowly. A concentration below the assay's quantification limit means no measurable plasma silver at that threshold; it does not directly answer whether silver was retained locally or how it moved through tissues. The study did not directly assess local immune responses, cellular uptake, local tissue interactions, biodistribution or clearance pathways.
The study also cannot answer sex differences for the intravaginal route because that group included female mice only. More broadly, the authors' conclusion covers the tested formulation, doses, routes, endpoints and 12-week period: repeated administration was well tolerated, with no treatment-related adverse effects across assessed measures and no sex-related differences. Because the experiment was conducted in mice, it is a preclinical tolerability finding rather than a human safety result.
Taken together, the results support an absence of detected treatment-related effects under the tested conditions, not proof that toxicity or exposure was impossible. Questions about local tissue distribution, immune responses and effects beyond the 12-week period remain outside what this study directly measured.
Paper data and sources
Original title: Route- and sex-dependent toxicity of clinical-stage silver nanoparticles in mice.
Authors: Buerlan Yeerkenbieke, Osmane Camara, Ruxandra-Ioana Cipu et al.
Journal/Repository: Nanoscale
Status: Peer-reviewed
First online: 2026-10-08
DOI: 10.1039/d6nr00957c
Original paper · Full text