Neuroinflammation is a major cause of central nervous system (CNS) damage and can result in long-term disability and mortality. Therefore, the development of effective anti-neuroinflammatory agents for neuroprotection is vital. To our surprise, the naturally occurring molecule alantolactone (Ala) was reported to significantly inhibit tumor growth and metastasis as a result of its excellent anti-inflammatory effects. Thus, we proposed that it could also act as an anti-neuroinflammatory agent. Thus, in this study, a coculture system of BV2 cells and PC12 cells were used as an in vitro neuroinflammatory model to investigate the anti-neuroinflammatory mechanism of Ala. The results indicated that Ala downregulated the expression of proinflammatory factors by suppressing the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.
Particles that modify delivery characteristics are a focus of drug-loading research. Hydroxyapatite particles (HAPs) have excellent biocompatibility, shape controllability, and high adsorption, making them a potential candidate for drug-delivery carriers. However, there are still some defects in the current methods used to prepare HAPs. In order to avoid agglomeration and improve the drug-loading properties of HAPs, the present study provides a novel triethylamine (TEA)-capped coprecipitation template method to prepare HAPs at room temperature. In addition, pure water and anhydrous ethanol were used as solvents to investigate the capping effect of the small-molecule capping agent TEA during the synthesis of HAPs. The results showed that the HAPs prepared in the TEA ethanol system had a smaller particle size (150–250 nm), better dispersion and higher crystallinity. The results were significantly different from those of the conventional preparation methods without TEA. However, the hydroxyapatite crystal would agglomerate to a certain extent after being stored for a period of time, forming micro/nano-sized agglomerates of nanocrystals. FITR analysis and SEM observation showed that the capping effect of TEA promoted the formation of a smaller template and dispersed HAPs were quickly formed by dissolution and reprecipitation processes. The drug-loading experiments showed that the HAPs prepared in the TEA ethanol system had high drug-loading capacity (239.8 ± 13.4 mg·g−1) as well as an improved drug-release profile demonstrated in the drug-release experiment. The larger specific surface area associated with the smaller particle size was beneficial to the adsorption of drugs. After drying at 60 °C, TEA was evaporated from the HAPs which agglomerated into larger micron particles with more drug encapsulated. Thus, the effect of a sustained release was achieved. In the present research, a novel approach was developed by using triethylamine as the capping agent to prepare micro/nano-sized agglomerates of HAP nanocrystals with improved drug loading, which is predicted to have potential application in drug delivery.
Severe burn wounds are characterized by epithelial disruption and persistent inflammation, which impede re-epithelialization and heighten susceptibility to bacterial colonization and invasion, thereby posing serious clinical risks. To address these challenges, we developed an innovative smart hydrogel (Ag-IMP-U@Cur), in which uridine (U) is incorporated as a backbone-forming component via reversible boronate ester bonds with phenylboronic acid, thereby endowing the hydrogel with dual functions of acidic microenvironment responsiveness and promotion of re-epithelialization. The Ag-IMP complex serves as a structural scaffold that reinforces the network stability, while the combination of Ag-IMP and Cur-loaded ZIF-8 (Cur-ZIF-8) imparts controlled-release, antibacterial, and anti-inflammatory properties. In vitro and in vivo studies demonstrate that this hydrogel markedly suppresses infection and inflammation while accelerating wound closure. Collectively, this work introduces an innovative strategy that integrates a nucleoside unit, metal ions, and a phytochemical into a responsive multifunctional hydrogel, offering a promising therapeutic avenue for severe burn injuries.