Ischemic stroke is a difficult-to-treat brain disease that may be attributed to a limited therapeutic time window and lack of effective clinical drugs. Nasal–brain administration is characterized by low systemic toxicity and is a direct and non-invasive brain targeting route. Preliminary studies have shown that the volatile oil of Chaxiong (VOC) has an obvious anti-ischemic stroke effect. In this work, we designed a nanoemulsion thermosensitive in situ gel (VOC-NE-ISG) loaded with volatile oil of Chaxiong for ischemia via intranasal delivery to rat brain treatment of cerebral ischemic stroke. The developed VOC-NE-ISG formulation has a suitable particle size of 21.02 ± 0.25 nm and a zeta potential of −20.4 ± 1.47 mV, with good gelling ability and prolonged release of the five components of VOC. The results of in vivo pharmacokinetic studies and brain targeting studies showed that intranasal administration of VOC-NE-ISG could significantly improve the bioavailability and had excellent brain-targeting efficacy of nasal-to-brain delivery. In addition, the results of pharmacodynamics experiments showed that both VOC-NE and VOC-NE-ISG could reduce the neurological deficit score of model rats, reducing the size of cerebral infarction, with a significant effect on improving ischemic stroke. Overall, VOC-NE-ISG may be a promising intranasal nanomedicine for the effective treatment of ischemic stroke.

Background: Anemoside B4 (AB4), the major bioactive saponin from Pulsatilla chinensis, exhibits anti-inflammatory, anti-tumor, anti-apoptotic, and analgesic properties. However, its clinical translation for ulcerative colitis (UC) is constrained by poor epithelial permeability and low oral bioavailability. Objective: This study’s objective was to engineer and optimize thermosensitive rectal in situ gels (ISGs) of AB4, incorporating suitable absorption enhancers to improve mucosal permeation, bioavailability, and therapeutic efficacy against UC. Methods: Screening of effective permeation enhancers was conducted using Caco-2 cell monolayers and Franz diffusion cells. Critical formulation variables such as poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) were optimized, employing single-factor experiments coupled with the Box–Behnken design response surface methodology (BBD-RSM). Comprehensive characterization encompassed in vitro release kinetics, in vivo pharmacokinetics, rectal tissue tolerability, rectal retention time, and pharmacodynamic efficacy in a UC model. Results: We used 2.5% hydroxypropyl-β-cyclodextrin (HP-β-CD) and 1.0% sodium caprate (SC) as the appropriate absorption enhancers, and the amounts of P407, P188, and HPMC were 17.41%, 4.07%, and 0.44%, respectively, to yield the corresponding in situ gels HP-β-CD-AB4-ISG and SC-AB4-ISG. The gel characterization, such as gelation temperature, gelation time, pH, gelation strength, etc., was in accordance with requirements. The ISGs did not stimulate or damage rectal tissue and remained in the rectum for a prolonged period. More importantly, an improvement in bioavailability and alleviation of UC were noted. Conclusion: Absorption enhancer-assisted, poloxamer-based thermosensitive rectal ISGs provide a safe, convenient, and effective platform for targeted delivery of AB4 to the colorectum. This strategy addresses key limitations of oral dosing and warrants further clinical development for UC and related colorectal inflammatory diseases.

To explore the changes in quality formation during the honey-processing of Glycyrrhiza uralensis from six geographical origins, including Inner Mongolia, Xinjiang, Anhui, Gansu, Guangdong, and Jiangxi. In this study, raw G. uralensis was mixed with honey and smoldered, then heated and stir-fried, and finally cooled. The water-soluble components (WSCs) and methanol-soluble components (MSCs) in G. uralensis were simultaneously analyzed by sequential electrospray ionization mass spectrometry (SESI-MS) without the need for complex sample pretreatment. Fifteen WSCs (e.g., proline, arginine, serine, glabrol, monosaccharides, disaccharides, and trisaccharides) and twenty-eight MSCs (e.g., liquiritigenin, naringenin, glycyrrhizic acid, glycyrrhetinic acid, and formononetin) were identified within 2 min. Both principal component analysis and partial least-squares discrimination analysis showed that samples of honey-processed G. uralensis (HPGU) from six different geographical origins were effectively distinguished; liquiritin, daidzein, sinapic acid, and ferulic acid were identified as potential differential metabolites by variable importance for the projection; and the contents of saccharides, glabridin, formononetin, glabrol, and glycyrrhetinic acid were high in HPGU. Meanwhile, Inner Mongolia showed the highest contents of glycyrrhetinic acid and daidzein, suggesting these samples may possess superior quality based on these specific markers. SESI-MS could enhance our understanding of the changes in quality formation during the honey-processing of G. uralensis.