Physical Characterization and Safety Evaluation of Folic Acid-conjugated Mesoporous Silica Nanoparticles Loaded with Rhodojaponin III

Background Rhodojaponin III (RJ-III), a characteristic diterpene of Rhododendron molle G. Don, has a wide range of pharmacological activities including anti-inflammatory, antihypertensive, and analgesic effects. However, further research and development have been limited because of its intense acute toxicity and poor pharmacokinetic profile. Objective In this study, we propose the construction of folic acid-conjugated mesoporous silica nanoparticles (FA-MSNs) as carriers to deliver RJ-III in an attempt to reduce acute toxicity and improve biomedical applications by prolonging drug release and targeting delivery. Methods FA-MSNs were synthesized and characterized. RJ-III was then loaded into FA-MSNs (RJ-III@FA-MSNs), and the in vitro drug release profile was assessed. Subsequently, the RJ-III@FA-MSNs' cytotoxicity and targeting efficiency were explored in lipopolysaccharide-activated RAW 264.7 cells, and their acute toxicity was investigated in mice. Results Spherical FA-MSNs were approximately 122 nm in size. Importantly, the RJ-III@FA-MSNs showed prolonged RJ-III release in vitro. Moreover, in lipopolysaccharide-activated RAW 264.7 cells, RJ-III@FA-MSNs not only reduced the cytotoxicity of RJ-III (P < 0.01), but also showed a good targeting effect from the results of cellular uptake. Additionally, the acute toxicity results demonstrated that RJ-III@FA-MSNs improved the LD50 value of RJ-III in mice by intraperitoneal injection 10-fold. Conclusion This is the first study to use FA-MSNs as carriers of RJ-III to reduce the acute toxicity of RJ-III. The results confirm the potential for targeted delivery of RJ-III in inflammatory cells to enhance efficacy, as well as providing data for future investigations on anti-inflammatory activity.