Meloxicam (MLX) is one of the most effective NSAIDs, but its poor water solubility and low bioavailability limit its clinical application. In this study, we designed a thermosensitive in situ gel of the hydroxypropyl-β-cyclodextrin inclusion complex (MLX/HP-β-CD-ISG) for rectal delivery to improve bioavailability. The best method for preparing MLX/HP-β-CD was the saturated aqueous solution method. The optimal inclusion prescription was optimized using an orthogonal test, and the inclusion complex was evaluated via PXRD, SEM, FTIR and DSC. Then, MLX/HP-β-CD-ISG was characterized regarding the gel properties, release in vitro, and pharmacokinetics in vivo. The inclusion rate of the inclusion complex obtained via the optimal preparation process was 90.32 ± 3.81%. The above four detection methods show that MLX is completely embedded in the HP-β-CD cavity. The developed MLX/HP-β-CD-ISG formulation has a suitable gelation temperature of 33.40 ± 0.17 °C, a gelation time of 57.33 ± 5.13 s, pH of 7.12 ± 0.05, good gelling ability and meets the requirements of rectal preparations. More importantly, MLX/HP-β-CD-ISG significantly improved the absorption and bioavailability of MLX in rats, prolonging the rectal residence time without causing rectal irritation. This study suggests that the MLX/HP-β-CD-ISG can have a wide application prospect with superior therapeutic benefits.
Introduction: The gut contains a diverse array of commensal microorganisms, forming a vital biological barrier within the intestine that contributes to the overall intestinal mucosal barrier. However, research on the rectal barrier during early development remains limited. This study aims to investigate the relationship between intestinal microbiota and rectal barrier function in young rats.Methods: We evaluated the rectal barrier structure and function in rats at 2-, 4-, and 10-week-old. Methodology included histological analysis, Muc2 expression quantification, immunofluorescence localization of tight junction proteins (ZO-1, Occludin, Claudins), blood glucose monitoring after rectal insulin administration, and 16S rDNA sequencing of rectal microbiota. Spearman correlation analysis was used to explore mechanisms linking age-dependent changes in rectal permeability to microbiota dynamics.Results: Physiological rectal permeability was significantly higher in 2-week-old rats compared to 4- and 10-week-old rats (p < 0.01), although systemic biomarkers (LPS, D-LA, and LBP) showed no significant differences. The rectal microbiota exhibited marked age-dependent shifts in composition, α/β-diversity, and metabolic pathways, with increased abundance of beneficial taxa (e.g., Muribaculaceae, Akkermansia) in older rats. Correlation analysis revealed strong associations between reduced permeability, elevated Occludin expression, and microbiota maturation (R = 0.65, p < 0.001).Conclusion: This study demonstrates that age-dependent maturation of the rectal barrier is closely linked to microbiota composition and tight junction protein expression, providing insights into developmental mechanisms and potential strategies for pediatric rectal drug delivery.
6 April 2025 in International Journal of Biological Macromolecules
Cerium dioxide (CeO₂) nanozymes are capable of mimicking the activities of superoxide dismutase (SOD) and catalase (CAT), thereby facilitating the scavenging of reactive oxygen species (ROS). This study aims to synthesize CeO₂ nanozymes with different morphologies by controlling reaction conditions and to elucidate the relationship between morphology and antioxidant and anti-inflammatory activities of the same material. The successful preparation of CeO₂ nanozymes with different morphologies was confirmed by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Our findings revealed that CeO₂ nanotubes exhibited the strongest total antioxidant capacity. More importantly, all CeO₂ nanozymes with different morphologies demonstrated excellent ROS scavenging abilities and effectively inhibited the activation of the NF-κB signaling pathway, reduced phosphorylated p65 (P-p65) protein levels, and consequently decreased the release of pro-inflammatory cytokines such as IL-6. This study not only elucidates the structure-activity-anti-inflammatory efficacy relationship of CeO₂ nanozymes but also provides a significant theoretical basis for the development of novel anti-inflammatory nanomedicines.
Compounds containing sulfur are the primary components of anti-radiation drugs and represent a key focus in the innovative design and discovery of pharmaceuticals. The adverse effects of synthetic sulfur-containing radiation protective agents are significant concerns that cannot be overlooked. It is imperative to identify natural sulfur compounds that exhibit low toxicity and high efficacy as radiation protection agents. Cruciferous plants demonstrate notable resistance to ionizing radiation. The literature review revealed that Lepidii semen and Descurainiae semen, both of which are rich in sulfur compounds and the PI3K/AKT signaling pathway regulates radiation-induced oxidative stress, inflammation, and apoptosis. We speculate that the sulfur compounds of the Lepidii semen and Descurainiae semen may exert radiation protection by regulating the PI3K/AKT signaling pathway, and this hypothesis was supported by molecular docking analysis. The sulfur compounds (glucotropaeolin, gluconapin, glucoiberverin, glucocappasalin, tropeolin, etc.) demonstrate greater potential.