Preparation and Characterization of pH-Responsive Microspheres Based on Sodium Alginate and Polyether Amine: Loading and Release of Tryptophan-Derived Cationic Antimicrobials

In weakly alkaline environments (such as the human intestinal tract), the effectiveness of conventional antimicrobials may be limited; therefore, a series of cationic tryptophan fatty alcohol esterifications were designed and synthesized, and these compounds were found to possess excellent broad-spectrum antimicrobial properties and good biosafety. Among the agents, tryptophan dodecyl ester (L-Trp-Z12) exhibited the highest antimicrobial efficacy, achieving minimal inhibitory concentrations of merely 0.30 mu g/mL against Staphylococcus aureus and 0.60 mu g/mL against Escherichia coli, and it caused 50% hemolysis at a concentration of 167 mu g/mL. Moreover, based on these cationic antimicrobial agents, a pH-responsive controlled release microsphere was designed and fabricated using SA and T403 as critical constituents. The composition, morphology, controllable release properties, and in vitro antimicrobial properties of the microspheres were systematically investigated. Microsphere SA/T403-2, which features a distinct surface topology with grooves and folds, achieved an encapsulation efficiency of 91.38% and a drug loading capacity of 4.02%. Additionally, the cumulative release rate in the first 10 h was 62% at pH 7.4 (simulated intestinal fluid), which was twice as high as at pH 1.2 (simulated gastric fluid), indicating the microspheres' pH-responsive behavior. The SA/T403-L-Trp-Z12 microspheres demonstrated excellent antibacterial effects against S. aureus. Therefore, the SA/T403-L-Trp-Z12 microspheres prepared in this study have promising applications in the field of drug carriers and antimicrobials for targeted drug delivery to the colon, providing valuable insights into the design of pH-responsive microspheres.