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.

二甲酸钾 (KDF) 是一种新型抗生素替代品。为了实现KDF的控释并延长其抗菌作用，采用尖孔凝固浴制备海藻酸钠（ALG）/魔芋葡甘露聚糖（KGM）/乙基纤维素（EC）/沸石P复合水凝胶抗菌微球。以水凝胶的溶胀率为响应值，进行Plackett Burman（PB）设计实验，结果表明ALG、KGM、沸石P和氯化钙（CA）是最重要的影响因素。然后进行最陡上升试验以逼近最大响应面积，采用响应面分析方法建立连续变面模型，研究水凝胶微球的构效关系和溶胀性能。结果表明，影响因素从大到小依次为沸石P>ALG>KGM>CA，且ALG/CA、KGM/ALG和沸石P/ALG相互作用。体外释药行为表明，微球提高了载药率和包封率，防止了KDF在胃液中的过早释放。释放动力学也遵循 Ritger-Peppas 模型。在模拟胃肠环境下，体外抗菌试验表明，抗菌药物的最低抑菌浓度（MIC）并防止胃液中 KDF 过早释放。释放动力学也遵循 Ritger-Peppas 模型。在模拟胃肠环境下，体外抗菌试验表明，抗菌药物的最低抑菌浓度（MIC）并防止胃液中 KDF 过早释放。释放动力学也遵循 Ritger-Peppas 模型。在模拟胃肠环境下，体外抗菌试验表明，抗菌药物的最低抑菌浓度（MIC）大肠杆菌、金黄色葡萄球菌和枯草芽孢杆菌分别为 12 mg/mL、12 mg/mL 和 24 mg/mL，表明微球有效抑制了肠道内细菌的生长。我们的结果表明水凝胶微球可用作潜在的药物递送系统。