Intestinal Fluid Research Articles

Sulfobetaine/Alginate/Chitosan Supported Hybrid N‐Isopropylacrylamide Hydrogels: Composition‐Dependent Diffusion/Compression Properties and Theophylline/Diclofenac Sodium/Ciprofloxacin Release Kinetics

ABSTRACTPoly(N‐isopropylacrylamide) (N), poly([3‐(methacryloylamino)propyl] dimethyl(3‐sulfopropyl) ammonium hydroxide) (SB) and SB/N hydrogels were prepared using N,N′‐methylenebisacrylamide as crosslinker, while their hybrid semi‐/full‐IPNs N1A, N1C, N1CA, SB/N1A, SB/N1C, and SB/N1CA were synthesized in the presence of Alginate (A)/Chitosan (C). All the hydrogels were evaluated by taking into account their appearances, compression strengths and swelling behaviors in the ranges of pH 1.2–9.0 and temperature 4°C–40°C. The compressive moduli of N and SB/N hydrogels increased from ~10 to 80 kPa by changing composition (from N, SB/N to N1CA, SB/N1CA), swelling solution (from DDW to PBS) and temperature (from 25° to 37°C). The release profiles of diclofenac sodium (DFNa), theophylline (Thp), and ciprofloxacin (CIP) from N, SB/N, and their semi‐/full‐IPNs were investigated at pH 1.2 and pH 7.4, mimicking gastric and intestinal fluids. Higuchi, Peppas, and Weibull models were used, to describe the mechanisms of DFNa, Thp, and CIP releases from the hybrid IPNs of N and SB/N. The values of n (> 0.45) and β (> 0.75) at 37°C for Peppas and Weibull equations showed that DFNa and CIP releases from SB/N hybrids, which are more hydrophilic than IPNs of N, are mainly controlled by swelling/relaxation process.

Core-shell aerogel design for enhanced oral insulin delivery

Current protein-based therapies often rely on intravenous and subcutaneous injections leading to patient discomfort due to the need for frequent administration. Oral administration route presents a more patient-friendly alternative, but overcoming the challenge of low drug bioavailability remains paramount. This limitation is primarily attributed to protein degradation in the harsh gastric environment, enzymatic breakdown, and poor intestinal permeability. With their unique properties, such as high porosity and surface area, and easy scalability, aerogels offer a promising platform for oral delivery of therapeutic proteins. This study focused on the development and characterization of both conventional and core–shell aerogels derived from natural polysaccharides for the oral delivery of insulin, utilizing Humulin R® U-100 as the insulin source for the first time. Aerogels were produced via supercritical carbon dioxide (sc-CO2) drying of alginate gel beads. Scanning Electron Microscopy (SEM) images confirmed that the core–shell aerogels had higher uniformity in size and a more well-defined porous structure in comparison to conventional aerogels. Structural differences of two alginate sources were evaluated by Fourier Transform Infrared (FTIR) spectroscopy. A notable difference in encapsulation efficiencies was observed between conventional (12 %) and core–shell (53 %) aerogels, highlighting the superior carrier characteristics of the latter ones. In vitro insulin release profiles from the core–shell aerogels demonstrated their potential suitability for delivering regular/short-acting insulin therapeutics since only 30 % of insulin was released in Simulated Gastric Fluid (SGF) after 120 min, whereas 60 % of insulin was released in Simulated Intestinal Fluid (SIF) within the first hour followed by a sustained release stage.

Effects of Different Weak Small Organic Acids on Clofazimine Solubility in Aqueous Media

Background/Objectives: Clofazimine (CFZ) is a Biopharmaceutics Classification System (BCS) II drug introduced in the US market in 1986 for the treatment of leprosy. However, CFZ was later withdrawn from the market due to its extremely low aqueous solubility and low absorption. In the literature, the intrinsic solubility of CFZ has been estimated to be <0.01 μg/mL, and solubilities of its different salt forms in simulated gastric and intestinal fluids are <10 µg/mL. These are extremely low solubilities for the dissolution of a drug administered orally at 100–200 mg doses. Methods: In the present investigation, seven weak organic acids (adipic, citric, glutaric, maleic, malic, succinic, and tartaric) were tested by determining the aqueous solubility of CFZ as the function of acid concentration to investigate whether any of the acids would lead to the supersolubilization of CFZ. Results: There were only minimal increases in solubilities when concentrations of acids in water were increased up to 2.4 M. The solubilities, however, increased to 0.32, 1.23, and 10.68 mg/mL, respectively, in 5 M solutions of tartaric, malic, and glutaric acids after equilibration for 24 h at 25 °C. Crystalline solids were formed after the equilibration of CFZ with all acids. Apparently, salts or cocrystals were formed with all acids, except for glutaric acid, as their melting endotherms in DSC scans were in the range of 207.6 to 248.5 °C, which were close to that of CFZ itself (224.8 °C). In contrast, the adduct formed with glutaric acid melted at the low temperature of 77 °C, and no other peak was observed at a higher temperature, indicating that the material converted to an amorphous state. Conclusions: The increase in CFZ solubility to >10 mg/mL in the presence of 5 M glutaric acid could be called supersolubilization when compared to the intrinsic solubility of the basic drug. Such an increase in CFZ solubility and the conversion of the glutarate adduct to an amorphous state are being exploited to develop rapidly dissolving dosage forms.

Novel capsaicin hollow salt constructed by nanoemulsion-spray drying strategy with enhanced antioxidant stability and stronger salty sensation

Designing new salt products to reduce sodium intake while maintaining the desired saltiness by optimizing the structure of salt has become a popular strategy in today's efforts to promote salt reduction. To meet this need and promote a more healthy diet, capsaicin (CAP) hollow salt (HS) with enhanced antioxidant stability and stronger salty sensation were prepared by nanoemulsion-spray drying strategy using a wet Maillard conjugate from whey protein isolate (WPI) and gum arabic (GA). The hollow salts prepared from nanoemulsions containing 15% (w/v) salt and 3% (w/v) WPI-GA conjugate showed better microstructure, water content, solubility, and angle of repose. The novel CAP-encapsulated hollow salt (CAP@HS) with 3% (w/v) WPI-GA conjugate exhibited a higher encapsulation rate of 72.16 ± 1.32% for CAP, along with good antioxidant ability and thermal ability. In addition, the CAP@HS demonstrated superior release in the intestinal fluid and exhibited high bioaccessibility during simulated digestion. It is worth mentioning that CAP@HS exhibited a higher fluorescence signal in the in vitro Na+ retention assay conducted on porcine tongue, when compared to that of traditional salt and hollow salt. Combined with electronic tongue taste analysis and sensory evaluation, CAP@HS showed a stronger salty sensation. This will lead to new strategies for dual realization of sodium reduction and enhanced functionality for salt reduction products.

Unfolding bovine serum albumin decorated selenium nanoparticles crosslinking with chitosan: Achieve stabilization of Pickering emulsions gel and enhance resveratrol bioaccessibility.

Resveratrol (Res) is a natural polyphenol exhibiting anti-oxidant and anti-inflammatory activity. However, the applications of Res have been limited due to its low stability and water solubility. To enhance the bioaccessibility of Res, unfolding bovine serum albumin-modified selenium nanoparticles (UBSA@SeNPs) encapsulated within chitosan (CS)-coated Pickering emulsions (CS-UBSA@SeNPs-PE) were used to load Res. The results showed that Res-loaded CS(0.06 %)-UBSA@SeNPs-PE has small droplet size (16.13 μm), high gel properties and excellent antioxidant properties. During the simulated digestion process, CS reduced the release rate of Res from Res-loaded CS(0.06 %)-UBSA@SeNPs-PE (42.27 %) to reach a slow release effect. Importantly, Res could quickly release from CS-UBSA@SeNPs-PE within intestinal fluid or in the presence of chitosanase. In simulated absorption experiments, the intestinal permeability of Res in Res-loaded CS(0.06 %)-UBSA@SeNPs-PE were enhanced by 292.31 % compare to Res-loaded CS(0 %)-UBSA@SeNPs-PE. In pharmacokinetic studies, Res-loaded CS(0.06 %)-UBSA@SeNPs-PE had an area under the curve (AUC) up to 3467.99 ± 127.43 ng*h/mL. Furthermore, CS also improved the mucoadhesive nature of UBSA@SeNPs-PE, resulting in a gut-retention time of Res-loaded CS(0.06 %)-UBSA@SeNPs-PE that reached up to 60 h. In conclusion, CS-UBSA@SeNPs-PE can serve as an effective oral delivery system for improving the bioaccessibility of Res.

Immunomodulatory effects of inulin-type fructans from Arctium lappa L. by targeting gut microbiota and their metabolites

This study aimed to examine the in vitro digestion properties and immunomodulatory effects of inulin-type fructans (ALP-1) from Arctium lappa L. on immunosuppressive mice and to explore the underlying mechanisms. The simulated gastrointestinal digestion showed that ALP-1 underwent slight degradation during gastric and intestinal fluid digestion, with most of it reaching the gut as long-chain structures. The administration of ALP-1 effectively improved overall health and regulated immune function according to the spleen index, thymus index, splenic T-lymphocyte subsets, and other immune-related cytokines. Besides, 16S rDNA sequencing, ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry imaging technique revealed fructan-induced changes in gut microbiota composition, metabolic processes, and spatial information of key metabolites. These changes likely contributed to the immunomodulatory effects of ALP-1 in immunosuppressive mice. Therefore, ALP-1 shows promise as an immunomodulator for use in functional foods and nutraceuticals.

Preparation, characterization, stability, and antioxidant of quercetin-loaded hyaluronic acid complexes via pH-induced co-assembly

The purpose of this study was to investigate the feasibility of constructing an oral delivery system for quercetin (QUT) using hyaluronic acid (HA) as the wall material. The findings revealed that when the mass ratio of QUT to HA was 1:10, the prepared QUT-HA complexes exhibited excellent stability (particle size of 802 nm, zeta potential of -36 mV) and QUT loading capacity (encapsulation efficiency of 79.77%, loading capacity of 89.65 mg/g). The characterization of QUT-HA complex confirmed the formation of hydrogen bond between QUT and HA, resulting in a homogeneously dispersed coral-like complex and leading to the transformation of QUT's crystal structure into an amorphous state. Environmental stability analysis demonstrated that the QUT-HA complex maintains good stability within an ionic concentration range of 0-500 mM, a pH range of 3-8, and at temperatures of 50-90°C. In vitro simulations of gastrointestinal digestion indicated that the QUT-HA complex aggregates during simulated gastric fluid digestion and dissociates following simulated intestinal fluid digestion, effectively enhancing the bioaccessibility of QUT. Antioxidant assays showed that the scavenging ability of QUT against DPPH and ABTS radicals was significantly improved by complex loading. Therefore, the QUT-HA complex developed in this study possesses a high QUT loading capacity, excellent processing and digestive stability, and can effectively enhance the bioaccessibility and antioxidant activity of QUT, making it a promising candidate for use as an oral nutritional supplement in the field of functional foods.

Delivery of imiquimod to intestinal lymph nodes following oral administration

Intestinal lymph nodes are involved in the progression of colorectal cancer (CRC). Tumours suppress the activation of dendritic cells (DCs) in draining lymph nodes, diminishing anti-cancer immune response. Imiquimod (IMQ) facilitates DCs activation via toll-like receptor 7, suggesting that targeted delivery of IMQ to intestinal lymph nodes can improve the treatment of CRC. This study aims to enhance the delivery of IMQ to intestinal lymph nodes by a highly lipophilic prodrug approach. Amide prodrugs were synthesised by conjugating IMQ with saturated and unsaturated medium- to long-chain fatty acids. Their potential for intestinal lymphatic transport was assessed by their affinity to chylomicrons and solubility in long-chain triglycerides. Further selection of prodrug candidates was determined by resistance to enzymatic hydrolysis in intestinal lumen and release of IMQ in the lymphatics using fasting state simulated intestinal fluid supplemented with esterases, brush border enzyme vesicles and plasma. Key pharmacokinetic parameters and biodistribution in rats were assessed for the most promising compounds, prodrugs 5 and 8. The plasma concentration–time profile of IMQ following oral administration of the prodrugs was less erratic in comparison to the administration of unmodified IMQ. The lymph-to-plasma ratios of IMQ concentration increased 1.9- and 1.7-fold using prodrugs 5 and 8 in comparison to administration of unmodified IMQ, respectively. Importantly, the average concentration of IMQ in mesenteric lymph nodes (MLN) was 11.2- and 7.6-fold higher than in plasma following the administration of prodrugs 5 and 8, respectively. Additionally, the non-specific wide distribution of IMQ into various organs and tissues was reduced with prodrugs. This work suggests that the highly lipophilic prodrug approach can efficiently deliver IMQ to intestinal lymphatics. In addition, this study demonstrates the feasibility of an amide prodrug approach for intestinal lymphatic targeting.

Long-term stable water-in-oil-in-water emulsion for effective protection and sustained release of lysine-calcium using chitosan and hydroxypropyl methyl cellulose

The poor tolerance to gastric acid and low absorption of calcium supplements in the intestinal tract remain a serious limitation in applications. Herein, lysine-calcium (Lys-Ca) has been synthesized via the chelation of Lys and high-temperature calcination scallop shell powder (HCSP), and subsequently encapsulated in a carefully designed water-in-oil-in-water (W/O/W) emulsion with a high encapsulation efficiency of 93 % using chitosan (CS) and hydroxypropyl methylcellulose (HPMC). Owing to the interfacial film formed by CS and HPMC between the droplets, the resulting emulsion demonstrates good acid and thermal stability, as well as long-term stability even after 60 d of storage at 25 °C. Meanwhile, the emulsion effectively protects the encapsulated Lys-Ca from damage in simulated gastric fluid (SGF). with only about 20 % Lys-Ca escaping into SGF (after 4 h). In simulated intestinal fluid (SIF), it sustainedly releases with a 61 % ratio at 1 h under the influence of bile salts and lipase, and near-complete release occurred after 6 h. Additionally, the emulsion presents no cytotoxicity and possesses appreciable calcium transport capacity. This work provides a well-designed double-emulsion strategy that offers a promising approach for developing efficient calcium supplements, aiming at improving the bioavailability of biomass calcium.

Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery

Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.

Encapsulation of ferulic acid in potato protein-pectin nanocomplexes with improved stability and controlled release properties

In this study, the potato protein (PP)-pectin (PC) nanoparticles were constructed to encapsulate ferulic acid (FA). The effects of FA additive amount, addition order and pH value on the properties of PP-FA-PC/PP-PC-FA nanocomplexes were investigated. It was found that when the mass ratio of PP to FA was 25:1, the PP-FA-PC nanocomplex had the smallest particle size, turbidity and the highest FA encapsulation efficiency. At pH 5.0, the addition order of FA had an effect on the properties of the nanocomplexes, and the formed nanocomplexes had larger particle size, higher turbidity and better encapsulation efficiency than the nanocomplexes formed at pH 7.0. Additionally, the nanocomplexes formed at pH 5.0 also possessed lower ABTS+ and DPPH free radical scavenging rates, indicating that FA was successfully encapsulated by PP-PC nanoparticles. The results of Z-average diameter and fourier transform infrared spectra confirmed PP-FA-PC nanocomplex at pH 5.0 encapsulated FA based on hydrogen bonding, hydrophobic and electrostatic interactions. The scanning electron microscopy showed that the PP-FA-PC nanocomplex exhibited irregular and segregated small particles at pH 5.0. Moreover, the PP-FA-PC nanocomplexes at pH 5.0 had the best encapsulation ability and protection effect on FA, and the environmental stability was the best. The release rate of FA loaded by PP-PC nanoparticles was greatly reduced in simulated gastric fluid, while increased in simulated intestinal fluid compared to free FA. This study may provide valuable information for PP-PC nanoparticles as a food-grade delivery system, signifying the potential application in the health food industry.

Enhancement of Digestive Enzyme Activity in Enterococcus faecalis Using ARTP Mutagenesis

Enterococcus faecalis is used as a probiotic in animal and human food supplements. Atmospheric and room temperature plasma (ARTP) systems have frequently been used to screen for effective mutant probiotics. In this study, E. faecalis was treated with ARTP, and high-yielding digestive enzyme mutant strains were obtained by measuring the activities of α-amylase, lipase, and neutral protease. A total of 833 mutant strains were obtained after 40–60 s of ARTP treatment, and after screening for digestive enzyme activity, EF-448, EF-798, and EF-804 were obtained. The three strains demonstrated an 180% increase in α-amylase activity, a 30% increase in lipase activity, and a more than 40% increase in neutral protease activity. Furthermore, the enzyme activities remained stable after nine generations. In addition, the strains exhibited high auto-aggregation capacity (over 91%) and high cell hydrophobicity (over 93%). After exposure to simulated intestinal fluid for 6 h, the survival rates of EF-448 and EF-798 were 85.71% and 82.32%, respectively. Moreover, the three mutant strains retained antioxidant capacity and DPPH free radical scavenging ability, and there was no hemolysis. A safety experiment has shown that there is no mortality of Macrobrachium rosenbergii within 14 days after receiving injections of mutant strains at different concentrations. In conclusion, this study obtained three mutant strains with high production of digestive enzymes and stable inheritance through ARTP mutagenesis of E. faecalis, providing an efficient microbial resource.

Impact of components of biorelevant media on solubilization of methotrexate and sulfasalazine by Pluronic F127

Pluronics are micelle-based solubilizers, improving the therapeutic potential of orally administrated drugs. In this connection, solubilizing action of Pluronics is being intensively studied in standard buffers simulating gastrointestinal fluids and consisting of inorganic components. However, human gastrointestinal fluids have more complicate composition due to the presence of organic compounds such as enzymes, mucus, and bile, which are able to form supramolecular aggregates and influence the solubilizing effect of Pluronics. Therefore, the use of specially designed biorelevant media is a promising approach to assessing the effectiveness of solubilizing activity of Pluronics in vitro.Based on this, we studied the solubilization of poorly soluble methotrexate and sulfasalazine, which are used in the treatment of autoimmune and oncological diseases, by Pluronic F127 in Fasted State Simulated Gastric Fluid and Fasted State Simulated Intestinal Fluid. Taurocholic acid and lecithin being the main components of these biorelevant media form micelles and thereby enhance the solubility of drugs that are insoluble or sparingly soluble in water. The affinity of drugs under consideration to the micelles of different nature, which are present in the dissolution medium, is examined in this work. The possible competing interactions of drug-micelle and drug-unimer are discussed in terms of the ionization state of drug molecules and the nature of surfactants.

Mesalamine loaded ethyl cellulose nanoparticles: optimization and in vivo evaluation of antioxidant potential in ulcerative colitis

This study aimed to optimize mesalamine (MES)-nanoparticles (NPs) using Box Behnken Design and investigate itsin vivoantioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose (EC) NP containing MES has particles size of 142 ± 2.8 nm, zeta potential (ZP) of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed NPs has a uniform and spherical shape. Thein-vitrorelease data disclosed that the EC NPs containing MES showed bursts release of 52% ± 1.6% in simulated stomach media within 2 h, followed by a steady release of 93% ± 2.9% in simulated intestinal fluid that lasted for 48 h. The MES release from NP best match with the Korsmeyer-Peppas model (R2= 0.962) and it followed Fickian diffusion case I release mechanism. The formulation stability over six-months at 25 °C ± 2 °C with 65% ± 5% relative humidity, and 40 °C ± 2 °C with 75% ± 5% relative humidity showed no significant changes in colour, EE, particle sizes and ZP. As perin vivoresults, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.

Complexation with Alginate in Pumpkin Leaf Protein Solutions for the Encapsulation of Folic Acid: The Effect of Extraction Protocols.

This study aimed to assess pumpkin leaves as a protein source and determine the feasibility of these proteins to form complexes with alginate for the encapsulation of folic acid. Different isolation protocols, two based on isoelectric precipitation (one with thermal pretreatment and the other with alkali pre-extraction) and one based on stepwise precipitation with ammonium sulfate, were compared regarding the yield and structural properties of the obtained leaf protein concentrates (LPC). The highest purity of protein was achieved using the thermal-acid protocol and the salting-out protocol at 40% saturation. RuBisCO protein was detected by SDS-PAGE in all LPCs, except for the fractions obtained through salting-out at saturation level ≥ 60%. Complexation of the LPC solutions (1 mg/mL) and sodium alginate solution (10 mg/mL) was monitored as a function of LPC:alginate ratio (2:1, 5:1, and 10:1) and pH (2-8) by zeta-potential measurements and confirmed by FT-IR analysis. Based on the results, the strongest interaction between LPCs and alginate occurred at a pH between 2.20 and 2.80 and an LPC:alginate ratio of 10:1. Complexation resulted in particle yields of 42-71% and folic acid entrapment of 46-92%. The LPC-folic acid interactions elucidated by computational protein-ligand docking demonstrated the high potential of RuBisCO as a biocarrier material for folic acid. The in vitro release study in the simulated gastrointestinal fluids indicated that complexes would be stable in gastric conditions, while folic acid would be gradually released in the intestinal fluids.

Improvement and Recovery of Intestinal Flora Disorder Caused by Ciprofloxacin Using Lactic Acid Bacteria.

In this study, four lactic acid bacteria (LAB) strains demonstrating ciprofloxacin, bile salt, gastric fluid, and intestinal fluid tolerance as well as adhesion ability to Caco-2 and HT-29 cells were used to improve and recover the intestinal flora disorders caused by ciprofloxacin, among which, Lactobacillus brevis 505 exhibited excellent adhesion ability to two kinds of cells and colonization ability to mouse intestinal. After ciprofloxacin treatment, certain recovery effect on cecum caused by ciprofloxacin in the mice was found during natural recovery (group 5C2), but it was challenging to fully restore the intestinal integrity to the initial level. After L. brevis 505 intervention (group 5C5), the intestinal damage to the colon and ileum caused by ciprofloxacin in mice was significantly alleviated; the recovery effect was better than that of natural recovery. Additionally, L. brevis 505 could effectively regulate INF-γ, sIgA, and RegIIIγ increase induced by ciprofloxacin. Shannon and Simpson index of the intestinal flora of mice in 5C5 group were higher than those in other group, the relative abundance of Bifidobacterium and Lactobacillus in the mice in 5C5 group was increased, indicating that LAB can better restore the structure and abundance of intestinal microflora. Consequently, L. brevis 505 shows promise as a probiotic for gut microbiota restoration and rebuilding during antibiotic therapy.

Comparative Analysis of Bare and Quercetin-Loaded Nonionic Block Copolymer Micelles in an Artificial Gastrointestinal Medium.

Block copolymer micelles have been increasingly used for the solubilization and delivery of hydrophobic drugs. There exists a possibility of dissociation of micelles and formation of other association structures in contact with the gastrointestinal fluid. In this study, we demonstrated the effect of the fed-state intestinal fluid (FeSSIF) upon characteristics of bare and quercetin (QCT)-loaded pluronic 123 (P123) micelles. Characterizations were performed using dynamic light scattering (DLS), 1H NMR, heteronuclear single-quantum coherence (HSQC), two-dimensional 1H-1H nuclear Overhauser effect spectroscopy (2D-NOESY), and diffusion-ordered spectroscopy (DOSY). In the case of bare micelles, we found copolymer-bile salt mixed aggregates without any noticeable change in size. DOSY data revealed that lecithin formed a separate aggregate in the FeSSIF. Complete micellar solubilization of QCT could be verified by the disappearance of its proton signals. At higher dose levels, the diffusion coefficient of micelles increased in the FeSSIF. We speculate that QCT-induced hydrophobicity and availability of FeSSIF components would have driven the formation of small-sized mixed assemblies. On the contrary, the diffusion coefficient of micelles decreased with an increase in the QCT load in the medium devoid of FeSSIF components. We deduce that lack of lecithin and bile salts precluded the formation of mixed assemblies in this case, and therefore, micelles turned heavier at higher QCT loads. Such insights on self-assembled formulations can be valuable in improving their biological performance.

Sodium Alginate-Starch Capsules for Enhanced Stability of Metformin in Simulated Gastrointestinal Fluids.

The use of biopolymers in pharmaceuticals is well established, particularly for encapsulating biologically active compounds due to their beneficial properties. Alginate, widely recognized for its excellent encapsulation abilities, is the most commonly used biopolymer, while starch, typically known as insoluble dietary fiber, also serves as an effective agent for trapping and protecting compounds during processing, storage, and gastrointestinal transit. Sodium alginate-starch capsules with varying compositions were analyzed to develop metformin hydrochloride (MET) containing capsules with adequate physicochemical properties. In vitro testing with simulated gastrointestinal fluids showed that after 1 h, capsules with equal amounts of alginate and starch had a higher swelling ratio and better drug release behavior, despite lower MET entrapment efficiency compared to other formulations. Microstructural analysis revealed stability in simulated gastric fluids and solubility in simulated intestinal fluids, key factors in drug development. The results suggest that these biopolymeric compositions are highly resistant to gastric fluids and minimally soluble in the intestines, making them suitable for extended drug release. This research evaluates key technological parameters of a cost-effective encapsulation method for the controlled release of active substances, providing a versatile solution for pharmaceutical and biomedical applications.

Understanding the Impact of Lipids on the Solubilizing Capacity of Human Intestinal Fluids.

Lipids in human intestinal fluids (HIF) form various structures, resulting in phase separation in the form of a lipid fraction and a micellar aqueous fraction. Currently used fed state simulated intestinal fluids (SIF) lack phase separation, highlighting the need for a deeper understanding of the effect of these fractions on intestinal drug solubilization in HIF to improve simulation accuracy. In this study, duodenal fluids aspirated from 21 healthy volunteers in fasted, early fed, and late fed states were used to generate 7 HIF pools for each prandial state. The apparent solubility of seven lipophilic model drugs was measured across these HIF pools, differentiating between the micellar fraction and the total sample (including both micellar and lipid fractions). The solubilizing capacities of these fluids were analyzed in relation to their composition, including total lipids, bile salts, phospholipids, total cholesterol, pH, and total protein. The solubility data generated in this work demonstrated that current fed state SIF effectively predicted the average solubility in the micellar fraction of HIF but failed to discern the considerable variability between HIF pools. Furthermore, the inclusion of a lipid fraction significantly enhanced the solubility of fed state HIF pools, resulting on average in a 13.9-fold increase in solubilizing capacity across the seven model compounds. Although the average composition of the fluids was consistent with previous studies, substantial variability was observed in micellar lipid concentrations, despite relatively stable total lipid concentrations. This variability is critical, as evidenced by the strong correlations between the solubilizing capacity of the micellar fraction and its micellar lipid concentrations. Additionally, this study identified that fluctuations in bile salt concentrations and pH contributed to the observed variability in micellar lipid concentration. In summary, the influence of the lipid fraction on solubility was 2-fold: it enhanced the solubility of lipophilic drugs in the total fluid, and contributed to the variability in the solubilizing capacity of the micellar fraction.

The regulatory effects of bioactive polysaccharides on intestinal function and bile acids: chemical structures, bioactivities, and mechanisms.

Polysaccharides are one of the important components of the human diet, offering a wide range of biological activities, especially in improving inflammation in the digestive system and addressing metabolic diseases. Among all the reported bioactivities of polysaccharides, their regulation effects on intestinal function and bile acids (BAs) are gradually attracting the attention of more researchers. Bile acids, the main components of intestinal lipid digestive fluid, are also key signal factors for metabolic homeostasis and impact overall health. Polysaccharides usually interact directly or indirectly with the gut and gut microbiota to participate in the regulation process of reabsorption, metabolism, and excretion of bile acids in humans, thereby exerting their role in the intervention of human diseases. In this review, we comprehensively reviewed the effects of bioactive polysaccharides on the regulation of intestinal function and bile acids. The chemical structures, bioactivities, and potential mechanisms for their activities were also reviewed. This study aimed to provide a comprehensive reference for future research on the activities and mechanisms of polysaccharides, as well as to offer important strategies and insights for the development of bioactive polysaccharides to prevent inflammatory and metabolic diseases.