Soy protein cold-set hydrogels as controlled delivery devices for nutraceutical compounds

The release of riboflavin from soy protein hydrogels of filamentous or particulate microstructure was investigated under gastric and intestinal conditions in the presence or absence of digestive proteases. Microscopic examination showed riboflavin arranged into crystals dispersed randomly throughout the gels. Rheological analysis revealed that the riboflavin load weakened the gel networks, which led to gel disintegration during hydro-swelling tests at pH 7.5. Dissolution tests showed that riboflavin release was faster at pH 7.5 than at pH 1.2 for both gels. Initial release was faster from particulate gels, due to their higher porosity and eroding granular texture. The release mechanisms involved in riboflavin release were diffusion and matrix degradation for both gels at pH 1.2 and pH 7.5. In the presence of pepsin at pH 1.2, both gel types provided good protection of riboflavin for at least 6 h, while both were digested in the presence of pancreatin at pH 7.5. These results suggest that both gels might be useful for transporting bioactive molecules through the gastrointestinal tract and delivering them in the small intestine. Considering their non-synthetic nature, they should be of great interest to developers of innovative functional foods.     

两种海藻酸钠基凝胶的溶胀和质构性能

壳聚糖、果胶和海藻酸钠是天然多糖,具有良好的生物相容性和生物可降解性等优点。以CaCl_2为交联剂制备壳聚糖-海藻酸钠水凝胶和果胶-海藻酸钠水凝胶,研究Ca Cl2浓度、多糖质量比(壳聚糖与海藻酸钠、果胶与海藻酸钠)和交联温度对水凝胶在模拟人体胃肠道环境(pH 1.2胃、pH 6.8小肠、pH 7.4结肠缓冲溶液)中溶胀性能的影响。当壳聚糖或果胶和海藻酸钠质量比为1.25∶1、CaCl_2浓度为0.09 mol/L、温度为60℃时,制备的水凝胶在pH 1.2溶液中溶胀率最小,在pH 6.8和pH 7.4溶液中溶胀率较大;结果表明所制备水凝胶具有pH值敏感性。此外,在优化条件下水凝胶具有较好的质构性能。     

大豆蛋白基复合水凝胶的制备及其体外释放

利用天然无毒的京尼平交联大豆蛋白(SB)和壳聚糖(CS)制备复合水凝胶(HD)控释载体,以茶碱(TP)作为药物模型,结合扫描电镜和核磁共振研究了复合凝胶的表观形态和结构,并对其在模拟胃肠液中的控释特性进行研究。结果表明:复合水凝胶中大豆蛋白和壳聚糖通过京尼平发生了明显的交联作用,并呈现紧密的网络结构。在pH1.2模拟胃液中,复合水凝胶的溶胀度和茶碱释放率较低,但在pH6.8模拟肠液中,却呈现较高的溶胀度和释放率。复合水凝胶在模拟胃肠液中120h内可实现对茶碱的可控释放。复合凝胶的释放特性不仅与SB/CS比例相关,而且还取决于添加的京尼平的含量。本实验结果说明了这种京尼平交联的复合凝胶较为适合用作药物在胃肠道中的定向运送载体。     

Maillard-Type Cross-Linked Soy Protein Hydrogels as Devices for the Release of Ionic Compounds: An In Vitro Study

The contribution of cross-linking degree on soy protein hydrogels release properties was studied in vitro using a Maillard-type cross linker and amaranth and methylene blue as tracers. Increased cross-linker concentration or salt presence in the gel generally led to decreased swelling/release rates in the absence of digestive enzyme. Surprisingly, at pH 1.2, amaranth was not released. In the presence of pepsin or pancreatin, increased cross-linker concentration or the presence of salt in the gel was also shown to decrease compound release, particularly for methylene blue at pH 7.5. Compound release was strongly dependent on medium pH and compound ionic status. Amaranth, an anionic molecule, showed slower release in gastric conditions, whereas methylene blue, a cationic drug, showed the opposite result. Partition coefficients of these compounds matched these results. This paper demonstrates the potential of food proteins as carriers of ionic compounds.     

Influence of ultrasound and enzymatic cross-linking on freeze-thaw stability and release properties of whey protein isolate hydrogel

This study investigated the effect of ultrasound and enzymatic cross-linking on the freeze-thaw (FT) stability and release properties of whey protein isolate hydrogels. We evaluated the FT stability by the changes in the microstructure, riboflavin retention, syneresis, water holding capacity (WHC), and texture of gels subjected to 3 FT cycles. High-intensity ultrasound (HUS) and transglutaminase (TGase)-mediated cross-linking improved the FT stability of whey protein isolate hydrogels loaded with riboflavin (WPISAR), as demonstrated by a more uniform and denser porous structure, significantly higher riboflavin retention, WHC, and textural properties, and lower syneresis after 3 FT cycles than those of untreated hydrogels. Furthermore, HUS- and TGase-mediated cross-linking decreased protein erosion and swelling ratio of WPISAR in simulated gastrointestinal fluids (SGIF) and reduced the riboflavin release rate in SGIF both with and without the addition of digestive enzymes. After 3 FT cycles, faster riboflavin release occurred due to a more porous structure induced by ice crystal formation compared with their unfrozen counterparts as detected by confocal laser scanning microscopy. High-intensity ultrasound- and TGase-mediated cross-linking alleviated the FT-induced faster riboflavin release rate in SGIF. High-intensity ultrasound- and TGase-treated gel samples showed that both diffusion and network erosion were responsible for riboflavin release regardless of FT. These results suggest that HUS- and TGase-mediated cross-linking improved the FT stability of WPISAR with a high riboflavin retention, and might be a good candidate as a controlled-release vehicle for riboflavin delivery to overcome undesired FT processing.     

Production of low-dosage lactose milk using lactase immobilised in hydrogel

A hydrogel based on chitosan was employed for the immobilisation of lactase with the aim of hydrolysing lactose and producing low-dosage lactose milk. The degree of swelling of the hydrogel was affected by the type of aqueous solution, pH and temperature. The lactase immobilisation capacities at pH 4.0 and pH 7.0 were 257.12 ± 3.18 and 157.87 ± 1.96 mg enzyme per g dried hydrogel, respectively, after 1440 min at room temperature. The activity of immobilised lactase ranged from 97.91 to 56.04 and 97.91 to 71.80% from the first to the tenth cycle of hydrolysis of standard lactose and lactose contained in UHT milk, respectively. Immobilised lactase in hydrogel could be applied for the production of low-dosage lactose milk for at least ten successive hydrolysis cycles. Moreover, hydrogels containing immobilised lactase could also be useful for the enzyme release in individuals with lactose intolerance.     

智能响应型水凝胶药物控释体系及其应用

本实验旨在构筑具有pH响应性能的生物基水凝胶药物缓释载体。以马来酸为离子交联剂,构筑了壳聚糖水凝胶（CS–Ma–Gel）;负载模型药物阿莫西林（Am）制备了载药水凝胶（Am/CS-Ma-Gel）,利用红外光谱、紫外光谱、扫描电子显微镜等表征了其结构和形貌并研究了其在不同pH介质中的溶胀性能和药物缓释性能。结果表明,Am较好地分散于CS–Ma–Gel水凝胶中,无分相现象;凝胶溶胀性能和药物缓释性能展现了pH响应性,在pH2.00、4.00、6.86和9.18的介质中,溶胀率分别为800%、2200%、760%和1300%;42 h累计Am释药率分别为24.6%、70.4%、35.7%和50.4%,释药能力与溶胀性能呈现正相关,而且酸性、碱性介质中的溶胀率、释药率高于中性介质。Am/CS-Ma-Gel制备方法简单、绿色,展现两性离子型pH响应水凝胶特性,为开发新型壳聚糖缓释材料奠定理论和实验基础。     

Modification of psyllium polysaccharides for use in oral insulin delivery

There is no doubt that fibers, in particular viscous dietary fibers, have positive effects on human health, both in the prevention and in treatment of chronic diseases. Psyllium, a medicinally important serum glucose reducing natural polysaccharide, if suitably tailored to prepare the hydrogels for controlled release of insulin; it can act as double potential candidate for cure of diabetes mellitus. Keeping in view the therapeutic importance of psyllium and its gel-forming nature we have prepared psyllium and methacrylamide based hydrogels by using N,N′-methylenebisacrylamide as crosslinker. The present paper discusses the effect of pH on swelling kinetics of the hydrogels and release dynamics of insulin from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the hydrogels. Non-Fickian diffusion mechanism has been observed for the release of insulin in pH 2.2 buffer and pH 7.4 buffer.     

Drug release from hydrogel containing albumin as crosslinker

Albumin is the major plasma protein and acts as a physiological carrier for various compounds including drugs. To take advantage of the drug-binding ability of albumin for a drug delivery system, we have prepared hydrogels consisting of acrylamide (AAm) and bovine serum albumin (BSA) by introducing three to four vinyl groups into one BSA molecule and subsequently copolymerizing it with AAm. The resultant hydrogel was solubilized by trypsin treatment, since BSA served as a crosslinker in the hydrogel. The BSA-crosslinked hydrogel (BSA-AAm hydrogel) was loaded with salicylic acid or sodium benzoate and their release was investigated. The BSA-AAm hydrogel released much more salicylic acid than sodium benzoate. In addition, the amount of released salicylic acid increased with the BSA content of the hydrogel, despite a decrease in the swelling ratio of the hydrogel. On the other hand, the amount of released sodium benzoate increased with the swelling ratio. When a hydrogel crosslinked with N,N'-methylenebis (acrylamide) was used as a control, both drugs showed release tendencies similar to that of sodium benzoate from the BSA-AAm hydrogel. Furthermore, the salicylic acid release was sustained longer on the BSA-AAm hydrogel than the sodium benzoate release. Taken together, it is thought that albumin in the BSA-AAm hydrogel preferentially adsorbs salicylic acid and contributes to the high drug loading and the sustained release of salicylic acid.     

A novel pH‐sensitive hydrogels for potential colon‐specific drug delivery: Characterization and in vitro release studies

Stimuli‐responsive hydrogels are extensively investigated to implement new biomedical and pharmaceutical approaches. In this work, novel pH‐sensitive semi‐interpenetrating polymer network (semi‐IPN) hydrogels based on starch and poly(aspartic acid) (PAsp) with potential applicability in the field of pharmaceutics were prepared and characterized. The goal was to obtain a colon specific drug delivery system and to exploit the pH‐sensitive behavior of the hydrogels. The obtained hydrogels were characterized by FTIR, thermogravimetric analysis (TGA), DSC, and SEM. The swelling behavior of the hydrogels with a suitable ratio of starch and poly(aspartic acid) was investigated in gastrointestinal simulated conditions. Moreover, the drug release studies were carried out using 5‐Flurouracil as a model of anticancer drug in enzyme free simulated gastrointestinal conditions and simulated intestinal conditions containing α‐amylase, respectively. The obtained hydrogels, due to their excellent pH‐sensitive release property, could be potentially used as drug delivery systems for the oral treatment of colonic cancer.     

pH响应性纤维素纳米纤丝/海藻酸钠基水凝胶的制备及其释药性研究

将纤维素纳米纤丝（CNF）和海藻酸钠（SA）共混,然后在CaCl2的交联作用下,制得具有pH响应性的CNF/SA水凝胶,并通过物理包裹的方式将阿司匹林（ASP）、CNF和SA三者混合均匀后,在CaCl2的交联作用下制得ASP/CNF/SA载药水凝胶,研究ASP在不同pH值环境中的缓释行为。结果表明,ASP/CNF/SA载药水凝胶的载药量为194 mg/g,包封率达49.9%,且药物分子和水凝胶都保持了很好的热稳定性。ASP/CNF/SA载药水凝胶的药物释放具有pH响应性,药物分子的释放速率随着环境pH值的升高而加快。在p H值为1.5～11.0的缓释条件下,药物的释放行为均为溶蚀作用。     

Fast‐swelling Superabsorbent Hydrogels from Poly(2‐hydroxy ethyl acrylate‐co‐sodium acrylate) Grafted on Starch

Fast‐swelling highly porous superabsorbent hydrogels were synthesized through a rapid radical polymerization under normal atmospheric conditions. To synthesize a biopolymer‐based superabsorbent hydrogel, 2‐hydroxyethyl acrylate (HEA) and sodium acrylate (AANa) were grafted on the starch backbone in an aqueous solution. The graft copolymerization reaction was carried out in the presence of ammonium persulfate (APS) as an initiator and ‐methylenebisacrylamide (MBA) as a crosslinker in a homogeneous medium. The chemical structure of the hydrogels was confirmed by FT‐IR spectroscopy and thermogravimetric analysis (TGA). The morphology of the samples was examined by scanning electron microscopy (SEM). The results indicated that with increasing the amount of sodium acrylate both swelling capacity and swelling under load (AUL) were increased. Preliminary swelling and deswelling behaviors of the hydrogels were also studied. The effects of pH and inorganic salt on the swelling behavior of the hydrogels were investigated as well.     

Formulation and in vitro evaluation of κ‐carrageenan‐pregelatinized starch‐based mucoadhesive gels containing miconazole

The aim of this work was to investigate the effects of using κ‐carrageenan (κ‐Carr) with pregelatinized starch (PGS) in the improvement of swelling and erosion behaviors of mucoadhesive gels containing 2% of miconazole. Polymer blends containing carrageenan and PGS were used for the formulation, and the effect of varying polymer concentrations on the drug release was studied. The matrices were prepared using different biopolymer (starch hydrogel) concentrations. Swelling and erosion characteristics of the matrices were carried out in various media and their impact on drug release were studied. The swelling action of the gel matrix was controlled by the rate of its hydration in the medium. Release studies have showed that the swelling and erosion of matrices influence the drug release. In addition, the presence of κ‐Carr in the gel formula improves the bioadhesive properties. The release data showed a good fit into the power law or Korsmeyer–Peppas equation indicating the combined effects of diffusion and erosion mechanisms of drug release. Most of the formulations released miconazole by an anomalous (non‐Fickian) transport mechanism, except those matrices that contained PGS alone which showed zero‐order release.     

Release of folic acid from sodium alginate-pectin-poly(ethylene oxide) electrospun fibers under in vitro conditions

The present study evaluated the release behavior of folic acid from ultrafine sodium alginate-pectin-poly(ethylene oxide) electrospun fibers under in vitro conditions. In aqueous solution, the release of folic acid at pH 1.2 (64%) was significantly higher than at pH 3 (21%). At pH 7.8, the majority of folic acid was released (97%) due to extensive swelling and partial dissolution of the fibers. In simulated gastric juice, the folic acid release profile was similar to that of aqueous solution at pH 1.2. By contrast, using the simulated pH 7.8 intestinal fluid, a lower amount (40%) of folic acid was released as compared with the aqueous alkaline solution. These results showed that the release of folic acid from the alginate fibers is affected by the constituents present in the simulated intestinal fluid, in addition to the pH effect. The in vitro release study showed that the composite alginate electrospun fibers have good potential as a carrier that retains folic acid in acidic food products (pH 3), but selectively releases the micronutrient in the small intestine.     

菠萝果肉纤维素水凝胶的制备及对益生菌的包埋与缓释分析

以菠萝果肉纤维素(pineapple pulp cellulose,PPC)为原料,利用离子液体1-丁基-3-甲基咪唑氯盐(1-butyl-3-methylimidazole chloride,BmimCl)作溶剂,溶解PPC制备菠萝果肉纤维素水凝胶(pineapple pulp cellulose hydrogel,...     

Food-grade filled hydrogels for oral delivery of lipophilic active ingredients: Temperature-triggered release microgels

Delivery systems are often needed to encapsulate lipophilic active agents, protect them during storage, and then release them within the mouth. In this study, gelatin and caseinate were used to fabricate temperature-sensitive filled hydrogel particles. Filled hydrogel microspheres were formed by electrostatic complexation of caseinate and gelatin in the presence of caseinate-coated lipid droplets. This was achieved by mixing aqueous 1% sodium caseinate and 1% gelatin solutions (volume ratio 1:2) at pH 5.8 with an oil-in-water emulsion. The majority of lipid droplets were trapped within the hydrogel microspheres. Turbidity and viscosity measurements of the hydrogels indicated that hydrogel particles dissociated upon heating because of gelatin melting (around 35 °C). Light scattering and confocal fluorescence microscopy indicated that lipid droplets were released from the gelatin-based hydrogel particles after oral processing, which was attributed to hydrogel melting under simulated mouth conditions. Our results suggest that hydrogel particles based on electrostatic complexation of sodium caseinate and gelatin could be useful as oral delivery systems for lipophilic active agents.     

燕麦蛋白-结冷胶冷诱导凝胶微观结构与控释特性的关联性研究

热变性后的燕麦蛋白(oat protein isolate,OPI)与结冷胶(gellan gum,GG)通过添加不同浓度的葡糖酸-δ-内酯(glucono-delta-lactone,GDL)形成OPI-GG冷诱导凝胶,通过质构分析、扫描电子显微镜、激光共聚焦显微镜以及傅里叶红外光谱,研究不同条件下形成的凝胶微结构以及分子构象的变化,探究不同凝胶微结构与凝胶控释特性的关联性。结果表明,在GG添加量为0.1%、pH 5时,凝胶硬度最大,随着GG浓度升高,凝胶硬度逐渐变弱。通过扫描电镜和激光共聚焦的观察可知OPI-GG凝胶可形成两种网络微结构,在pH 4和pH 5时,OPI与GG之间由于静电引力使其相互作用力增强,形成致密且均匀的单网络微结构;在pH 6和pH 7时,OPI与GG由于静电斥力的作用产生相分离,从而形成双网络结构。具有不同微结构的OPI-GG凝胶可作为基质包埋核黄素,双网络结构的凝胶可有效提高核黄素的包埋率(75%),其在pH 1.2磷酸缓冲溶液(phosphate buffer saline,PBS)中浸泡2 h后核黄素的释放率为33%;致密的单网络结构OPI-GG凝胶包埋率为61%,在pH1.2 PBS中可有效阻止核黄素的释放,其释放率为18%,并在pH 7.4 PBS中使核黄素逐步释放,8 h后释放率为53%。该研究结果表明,在中性条件下制备的OPI-GG双网络结构冷凝胶具有较好的核黄素包埋能力,在酸性条件下制备的OPI-GG单网络冷凝胶具有较好的控释能力,因此,不同微结构的OPI-GG冷凝胶具有作为营养素包埋和递送体系的潜力。     

Water sorption kinetics of superabsorbent hydrogels of saponified cassava starch‐graft‐poly(acrylamide)

Superabsorbent polymers (SAPs) are hydrophilic polymeric networks that can absorb, swell and retain large quantity of water and other physiological fluids. In this paper, the water sorption pattern and kinetics of cassava starch based SAP hydrogels were studied under different conditions of swelling such as soaking duration, pH, presence of salts, and particle size of the hydrogel. The kinetics was studied using Voigt‐based viscoelastic model to determine the rate parameter and the swelling rate (SR). It was noted that under all conditions, the water sorption followed a second order kinetics. The absorbency was directly proportional to the rate of swelling. But when the sample was allowed to swell in aqueous solutions of CaCl₂ and AlCl₃, the absorbency as well as the SR was irregular. The particle size also had significant effect on water absorption by the SAP and the polymer with smaller particles showed more absorption than those with larger particle size. The solvent induced phase transition of the superabsorbent hydrogel was also studied.     

Interactions between tea polyphenol and two kinds of typical egg white proteins—ovalbumin and lysozyme: Effect on the gastrointestinal digestion of both proteins in vitro

The promotion or inhibition of gastrointestinal digestion of tea polyphenol (TP) towards the two typical proteins from egg white (ovalbumin (OVA) and lysozyme (LYZ)) was examined. The results showed that TP made OVA/LYZ easier for digestion in the pepsin solution at pH 1.2 and inhibited OVA/LYZ digestion in pancreatin solution at pH 7.5. Non-covalent interactions between OVA/LYZ and TP and the secondary structure of OVA/LYZ were studied by using Fluorescence spectroscopy and Fourier transform infrared spectroscopy (FTIR), respectively. Results suggested that stronger conformational change occurred at pH 1.2 compared with that of pH 7.5 affected by TP in both proteins. Non-covalent interactions between OVA/LYZ and TP at pH 1.2 increased random and β-sheet structures in both proteins at the expense of α-helix, which resulted in the proteins with looser structures. At pH 7.5, an opposite second structural change of both proteins caused by the non-covalent interactions between OVA/LYZ and TP. The conformational and second structural change of proteins (substrate) might be a reason for promoting and inhibiting digestion of OVA/LYZ affected by TP.     

Dissolution tests as a tool for predicting bioaccessibility of nutrients during digestion

Bioaccessibility and bioavailability of active ingredients (like vitamins, antioxidants, etc.) into food systems is often compromised by factors like low permeability and/or solubility within the gut, lack of stability during food processing (temperature and oxygen) as well as in the gastrointestinal tract (pH, enzymes, presence of other nutrients). Moreover, little is known on the influence of food structure and breakdown in the gut on nutrient release. The possibility of predicting the release of nutrients from food matrices under simulated gastrointestinal conditions is of great relevance in order to define which food matrix is best for which nutrient, as well as for looking at the interaction of ingredients with the enzymes involved in the digestive process. This study explores the potential relevance of dissolution tests as a tool for predicting bioaccessibility of nutrients during in vitro digestion. Whey protein hydrogels containing green tea extract (GTE) were chosen for this study. Different simulated in vitro gastrointestinal conditions (GI) were applied throughout the dissolution experiments and the GTE was analysed by UV–vis absorption spectroscopy. It was possible to distinguish between two different release kinetics when experiments were performed in simulated gastric or intestinal media. In the gastric step, the kinetic of GTE release was lower than in an intestinal environment, suggesting that more GTE is released and available for absorption into the intestine than in the stomach. The present study shows that it is possible to use the dissolution tester as a screening method to mimic nutrient release from a food matrix in the gastrointestinal tract.