Comparative HPLC-MS/MS-based pharmacokinetic studies of multiple diterpenoid alkaloids following the administration of Zhenwu Tang and Radix Aconiti Lateralis Praeparata extracts to rats.

Abstracts Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0-∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

Exosome membrane-modified M2 macrophages targeted nanomedicine: Treatment for allergic asthma.

BACKGROUNDS: Exosomes are naturally secreted nanovesicles that have emerged as a promising therapeutic nanodelivery platform due to their specific composition, biological properties, and stability. Modifying synthetic nanoparticles with the intrinsic hallmarks of exosome membrane to create exosome mimetics could lead to safe and efficient smart silencer delivery. OBJECTIVES: The study focuses on exploring the combination of polylactic-co-glycolic acid (PLGA)-based nanoparticles with naturally occurring exosome membrane from M2 macrophages to deliver a Dnmt3aos smart silencer to treat allergic asthma (AA) in mice. MATERIALS AND METHODS: Exosome membrane of M2 macrophages and PLGA nanoparticles (PLGA NPs) wrapped with the smart silencer of Dnmt3aos (Dnmt3aossmart silencer) were first synthesized. The resulting exosome membrane coated PLGA@Dnmt3aossmart silencer (EM-PLGA@Dnmt3aossmart silencer) was administered intravenously into Der f1-induced asthma mice, which was followed by the investigation of therapeutic outcomes and the mechanism in vivo. RESULTS: Seven infusions of EM-PLGA@Dnmt3aossmart silencer ameliorated AA with a marked reduction of lung inflammation. After intravenous injection, the EM-PLGA@Dnmt3aossmart silencer was distributed in various organs, including the lungs, with retention over 48 h, and it targeted M2 macrophages. Moreover, the injections of EM-PLGA@Dnmt3aossmart silencer markedly decreased the proportion of M2 macrophages and inflammatory cytokines in the airway. More importantly, the EM-PLGA@Dnmt3aossmart silencer treatment did not obviously suppress the overall immune function of host. CONCLUSION: To our knowledge, this study provides the first experimental evidence of the ability of EM-PLGA@Dnmt3aossmart silencer to target M2 macrophages in the treatment of AA by combining exosome membrane and biomaterials, thus presenting a novel immunotherapy for the allergic disease.