pH-responsive drug-targeted delivery system: Dual-drug loading hollow mesoporous silica for synergistic therapy bacterial enteritis of Micropterus salmoides

Bacterial enteritis is a prevalent disease in Micropterus salmoides . Conventional drug delivery approaches are typically characterized by low efficiency and induce drug resistance. The present study synthesized mesoporous hollow silica nanoparticles (HMSS) and used physical adsorption to load enrofloxacin (ENR) and astaxanthin (ASX) onto the nanoparticles, achieving adsorption efficiencies of 77.39 % and 32.77 %, respectively. To establish the drug-targeted delivery system, ASX@HMSS was functionalized with cell-penetrating peptide (CPP) and ENR@HMSS was encapsulated with hydroxypropyl methylcellulose phthalate (HP55). Positive sustained-release effects were demonstrated by in vitro release studies, which demonstrated that the cumulative release rate of ASX@HMSS-CPP varied from 29.58 to 38.47 % at pH 6.5, whereas the cumulative release rate of ENR@HMSS-HP55 ranged from 70.19 to 88.25 %. The drug-targeted delivery nanoparticles extended the residence time of the drug in the intestines, according to in vivo pharmacokinetic investigations, and the overall metabolic profile was positive. Additionally, these drug-targeted delivery nanoparticles reduced intestinal inflammation and tissue damage, enhanced antioxidant and anti-inflammatory indicators, and improved the survival rate of Micropterus salmoides infected with enteritis. Following the administration of the drug-targeted delivery nanoparticles, the abundance of Aeromonas was significantly regulated, aiding gut microbial homeostasis. By controlling the PI3K-Akt, NF-κB, MAPK, and intestinal IgA immune network signaling pathways, the drug-targeted delivery nanoparticles also reduced intestinal inflammation. These findings demonstrate that the nanoparticle-based drug-targeted delivery system has potential applications in the prevention and treatment of diseases in aquatic animals.