Delivery of AgNP led to more pronounced local retention in the subcutaneous versus intraperitoneal location with limited uptake and toxic effects in rats

OBJECTIVE: To determine adverse effects of intraperitoneally (IP) or subcutaneously (SC) delivered silver nanoparticles (AgNP) in poloxamer 407 (P407; AgNP-P407) and local retention and systemic uptake in rats. STUDY DESIGN: Controlled randomized trial. ANIMALS: A total of 25 rats. METHODS: A total of 10 rats were randomly assigned in Phase 1 to a SC or IP surgical delivery group (5 rats/group) to receive 0.01 mg AgNP/rat in P407 (1:2 volume ratio). A total of 15 rats (5/group) were used in Phase 2 to receive IP: gel only (1.0 mL), AgNP-P407 (0.01 mg AgNP in 1.0 mL P407) or AgNP (0.01 mg in aqueous buffer). Incisions were assessed daily. Euthanasia was performed on day 7. The SC surgery sites and organs were harvested and evaluated histologically with scores reported. Plasma was obtained and batch analyzed together with organs for Ag content using mass spectroscopy. RESULTS: All rats survived the duration of the study. Minimal local histologic toxicity was seen after SC delivery. Plasma Ag peaked earlier for IP than SC delivery (p = .08) and for Ag delivered IP without gel (p = .04). Organ Ag uptake was minimal; macrophage aggregation was identified in the spleen and lymph node consistently. Rats that received P407 had increased cholesterol, whereas changes in total protein, albumin, glucose, amylase and lipase were seen for all groups. CONCLUSION: No adverse events were noted after use of AgNP-P407, while Ag uptake was delayed. CLINICAL RELEVANCE: Use of AgNP-P407 may be possible without systemic effects and prolonged local presence, but further testing is needed.