Chemopreventive Efficacy of Salvianolic Acid B Phospholipid Complex Loaded Nanoparticles Against Experimental Oral Carcinogenesis: Implication of Sustained Drug Release.

Background:Although we have previously demonstrated that phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating salvianolic acid B (SAB) can enhance anticancer activity in head and neck cancer and precancerous cells in vitro, the chemopreventive efficacy of SAB-PLC-NPs (nano-SAB) in vivo remains unclear. Here, we aimed to investigate the in vivo efficacy of nano-SAB against experimental oral carcinogenesis.Methods:Oral tongue carcinogenesis was induced in C57BL/6 mice through the administration of 4-nitroquinoline-N-oxide (4NQO, 100 µg/mL) in drinking water for 22 weeks. To preliminarily evaluate the effect of sustained drug release against oral carcinogenesis, free- or nano-SAB (16.6 mg/kg/d) was administered orally for 18 weeks, and the treatment was discontinued for the remaining 4 weeks.Results:Histological evaluation revealed a significant (P<0.05) decrease in the incidence of carcinoma in free-SAB-treated (16.7%) and nano-SAB-treated (10.0%) mice compared to mice exposed to 4NQO alone (34.3%). A decrease in carcinoma growth rate was also observed in free-SAB-treated (12.2%) and nano-SAB-treated (5.5%) mice compared to the 4NQO-exposed group (18.3%), even after drug withdrawal for 4 weeks. Immunohistochemical analysis revealed that nano-SAB treatment effectively suppressed Ki-67, proliferative cell nuclear antigen (PCNA), and cyclin D1 expression in high-risk dysplastic lesions compared to free-SAB-treated and 4NQO-exposed groups (all P<0.05). Importantly, nano-SAB maintained low levels of Ki-67, PCNA, and cyclin D1 expression even after drug withdrawal for 4 weeks.Conclusions:Together with our previous in vitro data, this in vivo study confirms that nano-SAB has superior chemopreventive efficacy by promoting more potent anti-proliferation and cell cycle arrest responses. These findings demonstrate the potential of SAB-PLC-NPs as promising chemopreventive agents for treating oral carcinogenesis.