Zein decorated rifaximin nanosuspension: approach for sustained release and anti-bacterial efficacy enhancement

<b>Aim:</b> The goal of the present work was to formulate zein-decorated rifaximin (RFX) nanosuspension to attain sustained release as well as effectiveness against <i>Escherichia coli (E. coli)</i>. <b>Methods:</b> The RFX nanosuspension was fabricated by using antisolvent addition method followed by coating using hydroalcoholic zein solution. The optimized RFX-NS and RFX-NS@zein was lyophilized for further spectroscopic evaluations. <i>In vitro</i> antibacterial potential was elucidated using well diffusion method whereas MIC value was determined by microbroth dilution method against <i>E. coli</i> for RFX-NS and pure RFX. <b>Results:</b> Box-Behnken Design was employed to assess the effects of independent variables on quality target product profile of RFX-NS. Optimized RFX-NS depicted particle size of 193.5 ± 4.45 nm with 76.49 ± 1.71% drug content. The significant change in particle size and zeta potential confirmed the formation of zein coated RFX-NS (RFX-NS@zein). <i>In vitro</i> release study depicted, 96.91 ± 1.21% release of RFX from RFX-NS in 6 h whereas 97.47 ± 1.99% RFX release was observed from RFX-NS@zein at the end of 12 h. Antibacterial assay of RFX-NS and free RFX against <i>E. coli</i> displayed MIC value of 15.44 ± 0.01 μg/ml and 72.96 ± 0.25 μg/ml, respectively. <b>Conclusion:</b> The results highlighted a significance of nanosuspension for improving the solubility of RFX and its antibacterial potential against <i>E. coli</i>. Rifaximin nanosuspension (RFX-NS) was prepared by antisolvent addition method owing to low solubility of RFX in aqueous phase. RFX-NS was coated with zein (RFX-NS@zein) to allow RFX-NS release in intestine. Box-Behnken design (3³) was utilized to evaluate the impact of formulation variables on particle size (nm), zeta potential (mV) and drug content (%). Compared with pure RFX, RFX-NS displayed significantly high aqueous solubility due to submicron particle size. Inhibitory concentration (IC₅₀) for RFX-NS was found to be significantly lower in comparison to pure RFX.

<b>研究目的：</b>本研究旨在制备玉米醇溶蛋白（zein）修饰的利福昔明（rifaximin，RFX）纳米混悬剂，以实现其缓释效果并增强对<i>大肠杆菌（Escherichia coli, E. coli）</i>的抗菌活性。<b>研究方法：</b>采用反溶剂添加法（antisolvent addition method）制备RFX纳米混悬剂，随后使用水醇玉米醇溶蛋白溶液（hydroalcoholic zein solution）进行包衣。将优化后的RFX-NS和RFX-NS@zein冻干（lyophilized），以开展进一步的光谱学评估（spectroscopic evaluations）。采用琼脂扩散法（well diffusion method）阐明其<i>体外</i>抗菌潜力，同时通过微量肉汤稀释法（microbroth dilution method）测定RFX-NS与纯RFX对<i>E. coli</i>的最低抑菌浓度（minimum inhibitory concentration, MIC）值。<b>研究结果：</b>采用Box-Behnken设计（Box-Behnken Design）评估自变量对RFX-NS质量目标产品概况（quality target product profile）的影响。优化后的RFX-NS粒径为193.5±4.45 nm，药物含量为76.49±1.71%。粒径与zeta电位（zeta potential）的显著变化证实了玉米醇溶蛋白包衣RFX-NS（RFX-NS@zein）的形成。<i>体外</i>释放研究显示，RFX-NS在6小时内释放96.91±1.21%的RFX，而RFX-NS@zein在12小时末释放97.47±1.99%的RFX。RFX-NS与游离RFX对<i>E. coli</i>的抗菌试验显示，其MIC值分别为15.44±0.01 μg/ml和72.96±0.25 μg/ml。<b>研究结论：</b>结果强调了纳米混悬剂在提高RFX溶解度及其对<i>E. coli</i>抗菌潜力方面的重要性。由于RFX在水相（aqueous phase）中的溶解度较低，采用反溶剂添加法制备利福昔明纳米混悬剂（RFX-NS）。用玉米醇溶蛋白包衣RFX-NS（RFX-NS@zein）以使其在肠道中释放。采用Box-Behnken设计（3³）评估处方变量（formulation variables）对粒径（nm）、zeta电位（mV）和药物含量（%）的影响。与纯RFX相比，RFX-NS因亚微米粒径（submicron particle size）表现出显著更高的水溶性。RFX-NS的半数抑制浓度（half inhibitory concentration, IC₅₀）显著低于纯RFX。