Mixed polyethylene glycol-modified breviscapine-loaded solid lipid nanoparticles for improved brain bioavailability: preparation, characterization, and in vivo cerebral microdialysis evaluation in adult Sprague Dawley rats.

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood-brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG2000) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration-time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 µg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 µg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG2000 had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.

Albiflorin Inhibits Advanced Glycation End Products-Induced ROS and MMP-1 Expression in Gingival Fibroblasts.

BACKGROUND: Periodontitis is a common complication of diabetes, with advanced glycation end products (AGEs) playing a key role in its pathogenesis. Albiflorin, a monoterpene glycoside, has shown potential anti-inflammatory and antioxidant properties. This study aims to investigate the effects of albiflorin on AGEs-induced gingival fibroblasts and its underlying mechanisms. OBJECTIVE: This study aimed to evaluate the role of albiflorin in mitigating ROS production, inflammation, and MMP-1 expression in AGEs-induced gingival fibroblasts. METHODS: The viability of gingival fibroblasts treated with albiflorin and AGEs was assessed using CCK-8 assays. ROS levels were measured by DCF staining, and the expression of inflammatory markers and MMP-1 was evaluated by ELISA and qPCR. The involvement of the NF-κB and Nrf2 pathways was examined by immunoblotting. RESULTS: Albiflorin enhanced the viability of AGEs-induced gingival fibroblasts and reduced ROS production. It also decreased the expression of IL-6, IL-8, RAGE, and MMP-1, suggesting an anti- inflammatory effect. Mechanistically, albiflorin modulated the NF-κB and Nrf2 pathways in AGEs-induced gingival fibroblasts. CONCLUSION: Albiflorin exhibited protective effects against AGEs-induced oxidative stress and inflammation in gingival fibroblasts, highlighting its potential as a therapeutic agent for periodontitis in diabetic patients. The modulation of the NF-κB and Nrf2 pathways by albiflorin provides insight into its mechanism of action.

[Comparison of the total arsenic concentration between saliva and blood after oral administration of sodium arsenite to rats].

OBJECTIVE: To compare the total arsenic concentration between blood and saliva after oral administration of sodium arsenite to SD rats. METHODS: A single oral gavage dose of sodium arsenite (20mg/kg) was administrated to 21 adult male Sprague-Dawley rats. Then collected blood and saliva samples at 0, 1-2, 4-5, 7-8, 11-12, 17-18, 23-24 hour for total arsenic detection. The blood samples were detected for total arsenic concentration by Atomic Fluorescence Spectrometry (AFS-230) and the salivary arsenic were detected by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: After intake of 20 mg/kg BW sodium arsenite, the total arsenic concentration in blood of SD rats was increased rapidly, and reached the peak value at the 1-2 hour, then descended gradually. However, there was a second peak value at the 7-8 hour. The upward trend of salivary arsenic was more slowly than blood arsenic, and reached the peak value at the 7-8 hour, then descended gradually. The variation tendency of salivary arsenic and blood arsenic with time were basically the same. Besides, there was an obvious positive association between them, the correlation coefficient was 0.678, P < 0.01. CONCLUSION: The excretion of arsenic in saliva was slower than that of blood samples after administrated a single oral gavage dose of sodium arsenite (20 mg/kg) to SD rate, but the metabolism mode of arsenic in saliva was similar with that in blood, suggested that salivary arsenic can also well reflect the exposure level of arsenic in the body.

Layer-by-layer immobilizing of polydopamine-assisted ε-polylysine and gum Arabic on titanium: Tailoring of antibacterial and osteogenic properties.

Bacterial infection has become a crucial reason that give rise to failure of medical implants in clinical applications. In this regard, various antibacterial surface modifications of implants have been developed in recent years. However, it remains a challenge to enable the implant surfaces with both suitable antibacterial and osteogenic properties. In this work, ε-polylysine and gum Arabic multilayer composite films were immobilized layer by layer (LBL) on anodized titanium with the assistance of polydopamine for the first time. In vitro antibacterial results showed that the bacteria numbers decreased with an increase in the loading amount of ε-polylysine. Furthermore, long-term antibacterial property up to 3 weeks against both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) was obtained combined with the merits of covalent binding and LBL methods. Meanwhile, the cell proliferation and osteogenic differentiation of BMSCs on titanium dioxide nanotubes (TNTs) modified with composite films was significantly improved. Remarkably, a facile method to optimize anti-infective and osteogenic properties of medical titanium has been developed, and it was demonstrated that the ε-polylysine and gum Arabic multilayer composite films with assistance of polydopamine were able to endow the orthopedic implant materials both improved antibacterial property and excellent biocompatibility, which is of profound significance for practical application of titanium-based implants.