Abstract

Potassium diformate (KDF) is a novel substitute for antibiotics. To achieve controlled release of KDF and extend its antibacterial effect, composite hydrogel antibacterial microspheres of sodium alginate (ALG)/konjac glucomannan (KGM)/ethyl cellulose (EC)/zeolite P were prepared using a sharp-hole coagulation bath. Considering the swelling rate of hydrogel as the response value, the Plackett Burman (PB) design experiment was performed to show that ALG, KGM, zeolite P, and calcium chloride (CA) were the most important influencing factors. Then, the steepest ascent test was performed to approach the maximum response area, and the response surface analysis method was used to establish the continuous variable surface model and investigate the structure-activity relationship and swelling property of the hydrogel microspheres. The results showed that the four factors in descending order of influence were zeolite P > ALG > KGM > CA, and that ALG/CA, KGM/ALG, and zeolite P/ALG interacted. In vitro drug release behavior showed that microspheres improved the drug loading rate and encapsulation efficiency, and prevented the premature release of KDF in gastric juice. The release kinetics also followed the Ritger-Peppas model. Under simulated gastrointestinal environment, in vitro antibacterial tests showed that the minimum inhibitory concentrations (MIC) of the antibacterial agents against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis were 12 mg/mL, 12 mg/mL, and 24 mg/mL, respectively, indicating that the microspheres effectively inhibited the growth of bacteria in the intestine. Our results indicated that hydrogel microspheres can be used as potential drug delivery systems.

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