Colon-targeted Delivery System Research Articles

Physicochemical, structural, and in-vitro release properties of carboxymethyl cellulose-based cryogel beads incorporating resveratrol-loaded microparticles for colon-targeted delivery system

The objective of this study was to investigate the physicochemical, structural, and in vitro release properties of carboxymethyl cellulose (CMC)-based cryogel beads incorporating resveratrol-loaded microparticles (MP) for colon-targeted delivery system. CMC-based cryogel beads were produced by ionic cross-linking with different concentrations (2%, 3%, and 4%) of AlCl3. Based on FE-SEM images, CMC-based cryogel beads showed a smoother surface and more compact internal structure with increasing AlCl3 concentrations, which was proven to be due to the new cross-linking between the –COO− group of CMC and Al3+ by FT-IR analysis. The encapsulation efficiency of the cryogel beads was significantly increased from 79.48% to 85.74% by elevating the concentrations of AlCl3 from 2% to 4%, respectively. In vitro release study showed that all CMC-based cryogel beads had higher stability for resveratrol than MP in simulated gastric conditions and can efficiently deliver resveratrol to colon without the premature release.

Current Update of Clinical Therapeutic Strategies for Colon-Targeted Delivery Systems

Oral colon-targeted drug delivery systems represent a significant advancement offering both systemic and local therapeutic effects for a range of intestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, colonic bacterial infections, and colorectal cancer. These systems facilitate the delivery of both small molecules and macromolecular compounds such as peptides, proteins, antibodies, oligonucleotides, RNA, and probiotics. This review provides an up-to-date exploration of the critical factors crucial for the effective design and development of drug delivery systems targeting the colon. The chosen strategy takes into account various aspects of colon physiology that influences the profile of drug release, absorption, dissolution, and stability in the colon, including pH, retention time, presence of enzymes, pressure, presence of reactive oxygen species due to inflammation, and specific receptors. Site-targeted drug release allows for high concentrations in the colon while minimizing systemic adverse effects by reducing or preventing drug absorption in the small intestine.

PREPARATION AND EVALUATION OF COLON-SPECIFIC PROBIOTIC DELIVERY SYSTEM: SACCHAROMYCES BOULARDII

Probiotics are beneficial microbes that have a beneficial effect on humans as well as animals. Despite their advantages, probiotics face viability challenges during storage and while passing through the upper gastrointestinal tract. This study was designed to develop an encapsulated system of Saccharomyces boulardii (SB) probiotics to overcome challenges with oral administration and develop a colon-targeted delivery system. Pectin and sodium carboxy methyl cellulose encapsulated microbeads of probiotics: polymer ratio (1:1, 1:2, and 1:3) were prepared using the ionotropic gelation technique and then coated with Eudragit® S 100 and cellulose acetate phthalate. They were then evaluated for efficacy and compared for bead size, flow properties, entrapment efficiency, percent yield, swelling index, mucoadhesive ness, in vitro release and viability of probiotics. The microencapsulated probiotics showed higher viability in the colon as compared to gastric and intestinal environments. Hence, microencapsulation is a potential delivery system for the administration of viable probiotics

Dual-Stimuli-Responsive Gut Microbiota-Targeting Nitidine Chloride-CS/PT-NPs Improved Metabolic Status in NAFLD.

Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease. The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing. The nanoparticles prepared in this study have an average particle size of (255.9±5.10) nm, with an encapsulation rate of (72.83±2.13) % and a drug loading of (4.65±0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice. This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.

Fabrication of hyaluronic acid-inulin coated Enterococcus faecium for colon-targeted delivery to fight Fusobacterium nucleatum

The abundance of Fusobacterium nucleatum (F. nucleatum) is highly associated with the development and poor prognosis of colorectal cancer (CRC), which is regarded as a promising target for CRC. However, until now, the novel strategy to clear F. nucleatum in the colon and CRC has not been well proposed. Herein, a probiotic strain Enterococcus faecium (E. faecium, EF47) is verified to secrete various organic acids and bacteriocins to exert superior antimicrobial activity towards F. nucleatum. However, the oral delivery of EF47 is affected by the complex digestive tract environment, so we design the hyaluronic acid-inulin (HA-IN) coated EF47 for colon-targeted delivery to fight F. nucleatum. IN can protect EF47 from the harsh gastrointestinal tract environment and is degraded specifically in the colon, acting as prebiotics to further promote the proliferation of EF47. The exposed HA can also enhance the targeting effect to the tumor area via the interaction with the CD44 receptor on the tumor cells, which is confirmed to increase the adhesive ability in tumor tissues and inhibit the growth of F. nucleatum. Therefore, this colon-targeted delivery system provides a novel platform to realize high-activity and adhesive delivery of probiotics to assist the therapeutic efficiency of CRC.

A pH-sensitive silica nanoparticles for colon-specific delivery and controlled release of catechin: Optimization of loading efficiency and in vitro release kinetics

Catechin is a naturally occurring flavonoid of the flavan-3-ol subclass with numerous biological functions; however, these benefits are diminished due to several factors, including low water solubility and degradation in the stomach's harsh environment. So, this study aimed to develop an intelligent catechin colon-targeting delivery system with a high loading capacity. This was done by coating surface-decorated mesoporous silica nanoparticles with a pH-responsive enteric polymer called Eudragit®-S100. The pristine wormlike mesoporous silica nanoparticles (< 100 nm) with high surface area and large total pore volume were effectively synthesized and modified with the NH2 group using the post-grafting strategy. Various parameters, including solvent polarity, catechin-carrier mass ratio, and adsorption time, were studied to improve the loading of catechin into the aminated silica nanoparticles. Next, the negatively charged Eudragit®-S100 was electrostatically coated onto the positively charged aminated nanocarriers to shield the loaded catechin from the acidic environment of the stomach (pH 1.9) and to facilitate site-specific delivery in the acidic environment of the colon (pH 7.4). The prepared nanomaterials were evaluated using several methods, including The Brauner-Emmett-Teller, surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope, Powder X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-ray Spectroscopy, and Differential Scanning Calorimetry. In vitro dissolution studies revealed that Eudragit®-S100-coated aminated nanomaterials prevented the burst release of the loaded catechin in the acidic environment, with approximately 90% of the catechin only being released at colonic pH (pH > 7) with a supercase II transport mechanism. As a result, silica nanoparticles coated with Eudragit®-S100 would provide an innovative and promising approach in targeted nanomedicine for the oral delivery of catechin and related medicines for treating diseases related to the colon, such as colorectal cancer and irritable bowel syndrome.

Fabrication of colon-targeted ethyl cellulose/gelatin hybrid nanofibers: Regulation of quercetin release and its anticancer activity

A colon-targeted delivery system that can efficiently deliver and release quercetin is essential to improve its bioavailability. We previously found that hydrophobic ethyl cellulose (EC) nanofibers could efficiently deliver quercetin to colon, but the release of quercetin was limited. To address this problem, hydrophilic gelatin (GN) was used as a regulator, and quercetin-loaded nanofibers with different mass ratios of EC to GN (3:1, 1:1, 1:2, 1:3) were fabricated by electrospinning. All nanofibers had a cylindrical morphology and high encapsulation efficiency (over 94 %), and there existed molecular interactions among quercetin, EC, and GN. The high GN content reduced the thermal stability of nanofibers but increased their surface wettability. Besides, these nanofibers had good stability in acidic and aqueous foods. Importantly, the release of quercetin in the simulated gastrointestinal fluid was <3 %. The addition of GN was beneficial to the release of quercetin in colon, and nanofibers with EC to GN being 1:3 had a more preferable release performance. The anticancer activity of nanofibers against HCT-116 cells was proved by inhibiting cell viability through the induction of apoptosis. Therefore, these nanofibers are potential carriers for efficient colon-targeted delivery of bioactive compounds in the food industry.

Prevention of Colitis-Associated Cancer via Oral Administration of M13-Loaded Lipid Nanoparticles.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease, is known to increase the risk of colitis-associated cancer (CAC). CAC has been found to be unresponsive to standard chemotherapy regimens, and the current treatments do not utilize effective small-molecule drugs and colon-targeted delivery systems. Previous studies indicated that the M13-nano-liposome (NL) formulation can effectively target the colon and reshape the gut microbiota in ex vivo cultures, generating altered microbial metabolites that can efficiently prevent chronic UC. In this study, we tested the cancer cell uptake ability of the NL formulation and investigated the potential of the M13-NL formulation to prevent CAC in the azoxymethane (AOM)-exposed IL10-/- mouse model. Our findings demonstrate that oral administration of M13-NL prevents tumor development in AOM-exposed IL10-/- mice, suggesting that M13-NL is a promising oral drug formulation for preventing CAC.

Multi-responsive starch-based nanocapsules for colon-targeting delivery of peptides: In vitro and in vivo evaluation

Colon-targeting delivery of insulin is surging great interests in revolutionizing diabetes. Herein, insulin-loaded starch-based nanocapsules developed by layer-by-layer self-assembly technology were rationally structured. Interactions between starches and the structural changes of the nanocapsules were unraveled to understand in vitro and in vivo insulin release properties. By increasing the deposition layers of starches, the structural compactness of nanocapsules increased and in turn retarded insulin release in the upper gastrointestinal tract. Spherical nanocapsules deposited at least five layers of starches could deliver insulin to the colon in a high efficiency according to the in vitro and in vivo insulin release performance. The underlying mechanism of the insulin colon-targeting release should ascribe to the suitable changes in compactness of the nanocapsules and the interactions between deposited starches after multi-response to the changes in pH, time and enzymes in gastrointestinal tract. Starch molecules interacted with each other much stronger at the intestine than that at the colon, which guaranteed a compact structure in the intestine but a loose structure in the colon for the colon-targeting nanocapsules. It suggested that rather than controlling the deposition layer of the nanocapsules, controlling the interaction between starches could also regulate the structures of the nanocapsules for colon-targeting delivery system.

Exploiting itraconazole-loaded nanomixed micelles in coated capsules as efficient colon-targeted delivery system for improved antifungal and potential anticancer efficacy

Chronic Inflammatory bowel diseases are usually accompanied by opportunistic colonic fungal infections. Itraconazole (ITZ), is a highly lipophilic broad-spectrum antifungal drug that is superiorly effective against several fungal species. Box-Behnken design was adopted to design ITZ-nanomixed micelles (ITZ-NMMs), aiming to enhance ITZ solubility, using various concentrations of Pluronic® L121, Cremophor EL, and with either sodium-deoxycholate or Pluronic® F68 through thin film hydration technique. Optimized formula composed of 90 % Pl–L121, 9.1% Cremophor EL, 3.127 % ITZ concentration and SDC as the hydrophilic surfactant and its particle size, Polydispersity index, zeta potential, entrapment efficiency, and release extent after 3 h were found to be 17.82 ± 0.189 nm, 0.26 ± 0.014, -6.72 ± 0.725 mV, 66 ± 7.4%, and 96.3 ± 7.22%, respectively. In vitro ITZ release study implied the ability of optimal ITZ-NMMs to enhance ITZ solubility in comparison to ITZ suspension. Also, augmented anti-fungal and anti-cancer activities were proven as ITZ-NMMs IC50 was 16.5 times that of pure ITZ. Afterwards, lyophilized optimal ITZ-NMMs formula was loaded into Eudragit S100-coated capsules where in vitro release and in vivo X-ray imaging ensured protection of ITZ release in either the stomach or intestine and targeting it to the colon. Such results suggested promising ITZ-NMMs system, capable of enhancing ITZ solubility in the intended target site, therefore, can be used not only in the treatment of colon fungal infections but also augments colon cancer therapy.

A colon-targeted delivery system of torularhodin encapsulated in electrospinning microspheres, and its co-metabolic regulation mechanism of gut microbiota

Torularhodin is a carotenoid with various biological activities. Carotenoids reportedly benefit gut health, but the effect of torularhodin on the gut is unclear. Therefore, torularhodin microspheres were prepared by electrospinning technology, and then their colonic targeting was studied by an in vitro intestinal simulation system. The results show that the torularhodin electrospinning nano-microspheres are highly stable in simulated gastric-small intestine digestion, but can be slowly released in the colon, owing to non-Fickian transport. The diversity and species abundance of gut microbiota after co-culture with torularhodin increased. Prevotella, Phascolarctobacterium, Ruminococcaceae UCG, Faecalibacterium, and Lachnospiraceae UCG were significantly more abundant, while Sutterella, Bacteroides, Escherichia, Collinsella and Intestinimonas were less abundant. Predictive functional results of gut microbiota indicated that torularhodin enhanced lysine biosynthesis of gut microbiota and decreased tyrosine metabolism. The metabolomics results also verified that the above pathways are the main metabolic pathways. Finally, the microbiota-host co-metabolic network clarifies that torularhodin can enhance key metabolites, such as l-lysine and l-carnitine in lysine biosynthesis, and inhibit key metabolites such as l-tyrosine and tyramine in tyrosine metabolism. The gut microbiota mainly involved in the positive regulation were Phascolarctobacterium, Prevotella, and Dialister, while the down-regulated microbes were Collinsella and Intestinimonas. This study demonstrates that torularhodin helps maintain the balance of the “host-gut” ecology, providing new applications for carotenoid-based diets to improve gut health.

Advances in Polysaccharide-Based Oral Colon-Targeted Delivery Systems: The Journey So Far and the Road Ahead.

Various colon-targeted oral delivery systems have been explored so far to treat colorectal diseases, including timed-release systems, prodrugs, pH-based polymer coatings, and microflora-triggered systems. Among them, the microbially triggered system has gained attention. Among various oral colon-targeted delivery systems discussed, the polysaccharide-based colon-targeted delivery system has been found to be quite promising as polysaccharides remain unaffected by gastric as well as upper intestine milieu and are only digested by colonic bacteria upon reaching the colon. The major bottleneck associated with this delivery is that non-suitability of this system during the diseased state due to decrease in bacterial count at that time. This causes the failure of delivery system to release the drug even at colonic site as the polysaccharide matrix/coat cannot be digested properly due to lack of bacteria. The co-administration of probiotics is reported to compensate for the bacterial loss besides facilitating site-specific release. However, this research is also limited at the preclinical level. Hence, efforts are required to make this technology scalable and clinically applicable.This article entails in detail various oral colon-targeted delivery systems prepared so far, as well as the limitations and benefits of polysaccharide-based oral colon-targeted delivery systems.

Encapsulation of propionic acid within the aqueous phase of water-in-oil emulsions: reduced thermal volatilization and enhanced gastrointestinal stability.

Propionic acid (PA) is a water-soluble substance that has been shown to be beneficial for improving colon-related diseases. However, its appliance as a nutraceutical ingredient is hampered by its volatility, irritating odor, and easy absorption in the stomach and small intestine. A chitosan solution containing propionic acid was dispersed in a palm oil/corn oil mixture with polyglycerol polyricinoleate (PGPR) to form PA-loaded water-in-oil (W/O) emulsions. The stability of the emulsions was improved by the inclusion of both chitosan and palm oil, where the chitosan reduced the emulsion particle size and palm oil increased the viscosity. The thermal volatility and storage stability of the encapsulated propionic acid were significantly improved due to the stability of emulsion structure and hydrogen bonding between chitosan and propionic acid. Around 56% of propionic acid remained within the aqueous phase after the simulated gastrointestinal digestion. Our results indicate that W/O emulsions might be candidates as colon-targeted delivery systems for propionic acid, which could be beneficial for maintaining colon health.

PH-responsive Pickering emulsions-pectin hydrogel beads for loading of resveratrol: Preparation, characterization, and evaluation

The present study aims to develop a novel resveratrol Pickering emulsions-pectin hydrogel beads (RSV-HB) colon targeting delivery system. The resveratrol-loaded Pickering emulsions were successfully incorporated into pectin hydrogel beads using the method of injection-gelation. The dynamic light scattering, scanning electron microscope, X-ray diffraction, and attenuated total reflection Fourier transform infrared spectroscopy were applied to investigate the effect of RSV-HB, and the result manifested that there had no impact on pectin. The stability study and the DPPH scavenging assay indicated that RSV-HB had credible physical stability. Additionally, the DPPH radical scavenging capacity of resveratrol was not influenced. In vitro dissolution study revealed that RSV-HB possessed the property of pH-responsive, colon targeting, and slow dissolution effect. Moreover, in vitro digestion study also presented that RSV-HB were able to sustain the digestion rate and targeted release. In summary, the RSV-HB are a promising delivery system for colon targeting application of resveratrol.

Polysaccharide, fecal microbiota, and curcumin-based novel oral colon-targeted solid self-nanoemulsifying delivery system: formulation, characterization, and in-vitro anticancer evaluation

The use of polysaccharides in preparation of microbially triggered colon-targeted delivery system has been explored extensively to deliver drugs at the colonic site. This type of targeting is attributed to inherent property of polysaccharides by virtue of which they are digested in the gut only by the colonic microflora. In last two decades, the use of fecal microbiota transplantation (FMT) has been reported widely to treat colonic diseases such as Crohn's disease, irritable bowel syndrome, and recurrent Clostridium difficile infection. It has been established that FMT downregulates inflammatory proliferation and pro carcinogenic pathways. Although a few reports exist on the use of colon-targeted FMT capsules in increasing the microbial diversity of gut microflora, they have not been able to establish clinical superiority of the colon-targeted capsules over conventional orally administered capsules. Hence, in the present study, an attempt has been made to utilize a multipronged strategy through a single formulation, wherein an anticancer phytoconstituent, polysaccharides, fecal microbiota extract (FME), and nanodelivery systems have been designed for the effective treatment of colon cancer. Overall, the study is aimed toward the development of an oral colon-targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) in which curcumin (CCM) was loaded. These SNEDDS were added to polysaccharide mixture of guar gum, pectin, lactose along with aerosol 200 (A-200) and then to the slurry of fecal microbiota extract. The liquid was then freeze dried and developed into solid SNEDDS powder. The process of formulating liquid SNEDDS was optimized using ternary phase diagram and Box Behnken Design. The developed formulation was characterized for physicochemical, physicomechanical, drug release and cytotoxic potential studies. The droplet size of reconstituted S-SNEDDS was found to be 78.46 ± 0.87 nm. The site-specific release of S-SNEDDS powder was confirmed by dissolution studies in medium containing rat caecal contents, wherein, the formulation containing guar gum and pectin in 1% w/w ratio showed less than 10% drug release in initial 5 h and burst release between 5th and 10th h indicating colon-specific release of CCM. Significant cytotoxic effect was seen for CCM-loaded S-SNEDDS as compared to control formulations. The use of 16s metagenomic technique confirmed no significant change in fecal microbiota composition of formulation pre- and postlyophilization. Overall, the study suggested a novel, oral colon-targeted SNEDDS-based formulation containing fecal microbiota and CCM for the treatment of colon cancer.

Controlling the Interaction between Starchy Polyelectrolyte Layers for Adjusting Protein Release from Nanocapsules in a Simulated Gastrointestinal Tract.

Orally delivered bioactive proteins face great challenges in the harsh environment of the upper gastrointestinal tract (GIT) in the field of functional foods based on bioactive proteins. Therefore, it is necessary to design carriers and delivery systems that have the potential to overcome the problem of lower bioaccessibility for protein cargoes. In this work, we present a starchy oral colon-targeting delivery system, capable of improving the release profile of the protein cargoes. The starchy oral colon-targeting delivery system was fabricated using layer-by-layer assembly of starchy polyelectrolytes (carboxymethyl anionic starch and spermine cationic starch) onto the surface of protein nanoparticles via electrostatic interaction. The dynamic change in the interaction between the starchy polyelectrolytes affected the shell aggregation structure and determined the release kinetics of nanocapsules in the GIT. Specifically, the stronger interactions between the starchy layers and the thicker and more compact shell layer kept the nanocapsule intact in the simulated gastric and intestinal fluids, better-protecting the protein from degradation by digestive fluids, thus avoiding the burst release effect in the SGF and SIF. However, the nanocapsule could quickly swell with the decreasing molecular interactions between starchy polyelectrolytes, increasing protein release (63.61%) in the simulated colonic fluid. Therefore, release behaviors of protein cargoes could be appropriately controlled by adjusting the number of deposited layers of pH-sensitive starchy polyelectrolytes on the nanocapsule. This could improve the bioaccessibility of oral targeted delivery of bioactive proteins to the colon.

A pH/Time/Pectinase-Dependent Oral Colon-Targeted System Containing Isoliquiritigenin: Pharmacokinetics and Colon Targeting Evaluation in Mice.

Oral colon-targeted gel beads containing isoliquiritigenin (ISL) were successfully designed in our study. In order to further explore the targeting of the colon by the gel beads, a systematic study of their in vivo pharmacokinetics and colon targeting was performed in mice. Eighteen male mice were included in this study. The mice were separated into six groups at random. We collected blood, stomach, duodenum, jejunum, ileum, and colon tissues at 2, 4, 6, 8, 12, and 24h after oral administration of gel beads containing isoliquiritigenin at a dose of 20mg/kg. Gel beads in tissues were recorded and taken out to observe their swelling and erosion. The total ISL concentrations in different tissues and gel beads were analyzed by high-performance liquid chromatography. All gel beads reached the upper part of the stomach at 2h with no obvious swelling. Most of the gel beads were still in the lower part of stomach, while a small amount had reached the small intestine at 4h. A few gel beads reached the colon and swelled at 6h. Furthermore, the gel beads in the colon were swollen and erosive at 8h. Meanwhile, the plasma ISL concentration could be detected, which indicated that the ISL in the gel beads was absorbed. At 12h, the gel beads were almost dissolved and the plasma concentration was 8.33 times that at 8 h. At 24h, the gel beads had completely disappeared, and the plasma concentration was 2.55 times that at 12h. The gel beads containing ISL are a sustained, controlled, and colon-targeting delivery system that can alter the ISL distribution in the gastrointestinal tract.

Novel pH-responsive polyvinyl alcohol/Arabic gum /magnesium oxide nanobiocomposite for oral colon targeted drug delivery

In this study, we used a novel pH-responsive polyvinyl alcohol/Arabic gum/magnesium oxide (PVA/AG/MgO nanobiocomposite) as an oral colon targeted delivery system for doxorubicin (DOX). Effect of different contents of PVA, AG and MgO NPs on drug loading efficiency, release behavior and kinetics of the prepared nanobiocomposite were investigated. A high loading efficiency of 82% was observed at 3 mg PVA,3 mg AG, and 6 mg MgO nanoparticles. The drug release from this nanobiocomposite was excellent pH-sensitive. The cumulative drug release could reach 90% in the simulated colonic environment (pH 7.4) within 10 h while lower than 10% of drug released in the simulated gastric environment (pH 1.2) at 2 h. In vitro cytotoxicity studies revealed that the PVA/AG/MgO nanobiocomposite was highly biocompatible. This study confirmed that novel PVA/AG/MgO nanobiocomposite has excellent potential for oral pH-sensitive delivery of drugs for the treatment of colon cancer and other colon diseases.

Curcumin loading and colon release of pectin gel beads: Effect of different de-esterification method

Low methoxyl citrus pectin (LMP) de-esterified from high hydrostatic pressure assisted enzymatic (HHP-pectin) and two other traditional methods was characterized, and curcumin-pectin calcium gel beads were prepared to study curcumin-loading and colon-targeted delivery abilities. It was found there was no significant difference among different LMP on amorphous structure, while significantly higher Rha/GalA ratio of HHP-pectin indicated higher rhamnogalacturonan Ⅰ (RG-I) proportion and branching extent. Curcumin was well embedded in LMP beads with improved stability. HHP-pectin beads showed significantly higher hardness, chewiness and encapsulation efficiency, while lower swelling ratio. Moreover, in vitro simulated digestion showed gel beads can deliver curcumin to colon and inhibit premature release. HHP-pectin beads could release curcumin more quickly in colon, probably because of differences on texture properties, which may be depended on molecular structure. Thus, LMP especially HHP-pectin calcium gel as colon-targeted delivery system for curcumin may have potential application in function food and drug delivery.

Fabrication of astaxanthin-enriched colon-targeted alginate microspheres and its beneficial effect on dextran sulfate sodium-induced ulcerative colitis in mice.

Astaxanthin (Ax) with a strong antioxidant activity is beneficial to human health, but its application is limited by its highly unsaturated structure and poor water-solubility. Ax-enriched colon targeted alginate particles (Ax-Alg) was prepared by high-pressure spraying and ionic gelation, and most of particles was in the range of 0.5-3.2μm in a diameter. The in vitro models showed that Ax-Alg can maintain the structural integrity in the different conditions (pH, heat and ion). In addition, Ax-Alg can well tolerate the conditions in the mouth, stomach and small intestine and reach the colon where Ax was released due to fermentation of gut microbiota. Mice experiment showed that Ax-Alg reduced dextran sulfate sodium-induced colitis, involving weight loss, disease activity index, colonic mucosal integrity and inflammation, and oxidative damage. On the other hand, Ax-Alg regulated the gut microbiota composition and reduced the abundances of Bacteroidetes members that had positive correlation with ulcerative colitis. Ax-Alg had better effect on the treatment of ulcerative colitis than oil-in-water emulsion, which can be attributed to the synergistic effect of Ax and alginate. This study can be helpful for the application of colon-targeted delivery system in the foods and treatment of colon diseases.