针对咖啡酸苯乙酯(caffic acid phenethyl ester, CAPE)难以在水中溶解、不稳定、易氧化的性质,该研究根据胃肠道环境的特点,将CAPE以CAPE-大麦醇溶蛋白纳米颗粒(CAPE-hordein nanoparticles,CAPE-HD)的形式负载到多孔淀粉中(CAPE-hordein nanoparticles/porous starch, CAPE-HD/PS),再包覆果胶-海藻酸钠形成水凝胶,形成pH和α-淀粉酶双响应药物控释体系(CAPE-hordein nanoparticles/porous starch-pectin-alginate, CAPE-HD/PS-PA),用于CAPE口服给药。对CAPE-HD/PS和CAPE-HD/PS-PA进行了结构、形态特性及其对CAPE的包封效果的考察,并对其进行了溶胀行为和释放行为的评价。结果表明,CAPE和大麦醇溶蛋白结合,以纳米颗粒的形式负载于多孔淀粉的表面和孔径内部,并随CAPE-HD/PS均匀分散于果胶和海藻酸钠交联成的三维水凝胶网络中。且CAPE在负载于复杂水凝胶之后,其存在状态发生了改变,凝胶中各组分之间不是简单的物理混合,而是以氢键等非共价作用力形成了新的结合物。水凝胶球呈现出在模拟胃液中“收缩”和模拟肠液中“溶胀”的溶胀特征。释放行为研究结果显示CAPE-HD/PS-PA具有pH和α-淀粉酶双重响应释放特性,有效实现了在胃液中对CAPE的保护和在肠道中的控释效果,有利于提高CAPE的分散度和生物利用度。CAPE-HD/PS-PA复杂水凝胶体系的开发,为CAPE等难溶性活性物质的临床使用提供新的开发方向,并为多孔淀粉和果胶等食用多糖类物质在药物或活性物质的口服递送领域提供依据和参考。
Caffic acid phenethyl ester (CAPE) was known as the characteristics that are difficult to dissolve in water, unstable and easily oxidized.To address this issue, in this study, according to the characteristics of the gastrointestinal environment, CAPE was loaded into porous starch (CAPE-HD/PS) in the form of CAPE-hordein nanoparticles (CAPE-HD), which was then coated with pectin-alginate to form the pH- and α-amylase-responsive dual-responsive drug controlled-release system (CAPE-hordein nanoparticles/porous starch-pectin-alginate, CAPE-HD/PS-PA), for the oral drug delivery of CAPE.CAPE-HD/PS and CAPE-HD/PS-PA were examined for their structure, morphology, and encapsulation effect on CAPE, and were evaluated for their swelling behavior and release behavior.Results showed that CAPE and hordein were combined and loaded as nanoparticles on the surface and inside the pores of porous starch, and uniformly dispersed in a three-dimensional hydrogel network cross-linked by pectin and alginate.Moreover, after loading onto the complex hydrogel, the state of existence of CAPE changed.Instead of simple physical mixing between the components in the complex, new conjugates were formed by non-covalent forces such as hydrogen bonding.The hydrogel spheres showed swelling characteristics of “contraction” in simulated gastric fluid and “swelling” in simulated intestinal fluid.The results of the release behavior study showed that CAPE-HD/PS-PA had the dual-responsive release characteristics of pH and α-amylase, which effectively realized the protection of CAPE in gastric fluid and the controlled release effect in the intestine, and was conducive to the improvement of CAPE dispersion and bioavailability.The development of the CAPE-HD/PS-PA complex hydrogel system provides a new development direction for the clinical use of difficult-to-soluble active ingredients, such as CAPE, and provides a basis and reference for edible polysaccharides, such as porous starch and pectin, in the field of oral delivery of drugs or active ingredients.
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