Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury.

Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

Polyvinylpyrrolidone-Polydatin nanoparticles protect against oxaliplatin induced intestinal toxicity in vitro and in vivo.

Oxaliplatin (OXL) is a first-line drug for the treatment of colon cancer, with excellent efficacy. Intestinal toxicity is a common side effect of OXL, with unclear pathogenesis and a lack of effective treatment strategies. Polydatin (PD) has anti-inflammatory and antioxidant activities and is a potential drug for treating intestinal diseases, but its poor water solubility limits its application. In this study, polyvinylpyrrolidone (PVP) was used as a carrier to prepare nanoparticles loaded with PD (PVP-PD), with a particle size of 92.42 nm and exhibiting sustained release properties. In vitro results showed that PVP-PD protected NCM460 cells from OXL induced injury, mitochondrial membrane potential (MMP) disruption, and accumulation of reactive oxygen species (ROS). The in vivo results demonstrated the protective effect of PVP-PD on intestinal toxicity induced by OXL, such as alleviating weight loss and colon length reduction induced by OXL. Both in vivo and in vitro mechanisms indicated that OXL induced DNA damage and activated the cGAS-STING pathway, further inducing the expression of inflammatory factors such as IL-1ß and TNF-α. PVP-PD alleviated the aforementioned changes induced by OXL by inhibiting the DNA damage-cGAS-STING pathway. In summary, our study demonstrated that the DNA damage-cGAS-STING pathway was involved in OXL induced intestinal toxicity, and PVP-PD provided a potential strategy for treating OXL induced intestinal toxicity.

Baicalein-loaded silk fibroin peptide nanofibers protect against cisplatin-induced acute kidney injury: Fabrication, characterization and mechanism.

Silk fibroin (SF) is a natural polymeric biomaterial widely used in the preparation of drug delivery systems. Herein, silk fibroin peptide (SFP) was self-assembled into nanofibers, encapsulated a poorly water-soluble drug baicalein (SFP/BA NFs), and then used to protect against cisplatin-induced acute kidney injury (AKI). Specifically, the SFP/BA NFs significantly enhanced the aqueous dispersity, storage stability, and in vitro antioxidant activity of BA. SFP/BA NFs increased the drug uptake and localization to mitochondria. In vitro results demonstrated that SFP/BA NFs can relieve the cisplatin-induced HK-2 cell damage, and inhibit the cisplatin-induced accumulation of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) disruption. Mechanism studies demonstrated that SFP/BA NFs may exert nephroprotective effects by inhibiting both the cisplatin-induced DNA damage and the cGAS/STING pathway activation. In vivo results showed that cisplatin treatment resulted in decreased body weight, increased serum creatinine (SCr), and increased blood urea nitrogen (BUN) levels, while SFP/BA NFs reversed the above symptoms. Furthermore, SFP/BA NFs reversed the cisplatin-induced abnormal changes of antioxidant enzymes (e.g., SOD and GSH), and inhibited the cisplatin-induced DNA damage as well as the activation of cGAS/TING. Above all, our results revealed the potential of SFP/BA NFs to protect against cisplatin-induced AKI.