Simulated Intestinal Fluid Research Articles

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

This study aimed to optimize MES-nanoparticles using Box Behnken Design (BBD) and investigate its in vivo antioxidant 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 nanoparticle containing mesalamine has particles size of 142 ± 2.8 nm, zeta potential of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed nanoparticles has a uniform and spherical shape. The in-vitro release data disclosed that the ethyl cellulose nanoparticles containing mesalamine showed bursts release of 52±1.6% in simulated stomach media within 2 hours, followed by a steady release of 93±2.9% in simulated intestinal fluid that lasted for 48 hours. The mesalamine release from nanoparticle 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 ± 2 °C with 65 ± 5% relative humidity, and 40 ± 2 °C with 75 ± 5% relative humidity showed no significant changes changes in colour, entrapment efficiency, particle sizes and zeta potential. As per in vivo results, MES-NP effectively increased GSH, 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.

Mirror-Image Random Nonstandard Peptides Integrated Discovery (MI-RaPID) Technology Yields Highly Stable and Selective Macrocyclic Peptide Inhibitors for Matrix Metallopeptidase 7.

Matrix metallopeptidase 7 (MMP7) plays a crucial role in cancer metastasis and progression, making it an attractive target for therapeutic development. However, the development of selective MMP7 inhibitors is challenging due to the conservation of active sites across various matrix metalloproteinases (MMPs). Here, we have developed mirror-image random nonstandard peptides integrated discovery (MI-RaPID) technology to discover innate protease-resistant macrocyclic peptides that specifically bind to and inhibit human MMP7. One identified macrocyclic peptide against D-MMP7, termed D20, was synthesized in its mirror-image form, D'20, consisting of 12 D-amino acids, one cyclic β-amino acid, and a thioether bond. Notably, it potently inhibited MMP7 with an IC50 value of 90 nM, and showed excellent selectivity over other MMPs with similar substrate specificity. Moreover, D'20 inhibited the migration of pancreatic cell line CFPAC-1, but had no effect on the cell proliferation and viability. D'20 exhibited excellent stability in human serum, as well as in simulated gastric and intestinal fluids. This study highlights that MI-RaPID technology can serve as a powerful tool to develop in vivo stable macrocyclic peptides for therapeutic applications.

Mirror‐Image Random Nonstandard Peptides Integrated Discovery (MI‐RaPID) Technology Yields Highly Stable and Selective Macrocyclic Peptide Inhibitors for Matrix Metallopeptidase 7

AbstractMatrix metallopeptidase 7 (MMP7) plays a crucial role in cancer metastasis and progression, making it an attractive target for therapeutic development. However, the development of selective MMP7 inhibitors is challenging due to the conservation of active sites across various matrix metalloproteinases (MMPs). Here, we have developed mirror‐image random nonstandard peptides integrated discovery (MI‐RaPID) technology to discover innate protease‐resistant macrocyclic peptides that specifically bind to and inhibit human MMP7. One identified macrocyclic peptide against D‐MMP7, termed D20, was synthesized in its mirror‐image form, D’20, consisting of 12 D‐amino acids, one cyclic β‐amino acid, and a thioether bond. Notably, it potently inhibited MMP7 with an IC50 value of 90 nM, and showed excellent selectivity over other MMPs with similar substrate specificity. Moreover, D’20 inhibited the migration of pancreatic cell line CFPAC‐1, but had no effect on the cell proliferation and viability. D’20 exhibited excellent stability in human serum, as well as in simulated gastric and intestinal fluids. This study highlights that MI‐RaPID technology can serve as a powerful tool to develop in vivo stable macrocyclic peptides for therapeutic applications.

Development of polymer-encapsulated microparticles of a lipophilic API-IL and its lipid based formulations for enhanced solubilisation

Active Pharmaceutical Ingredient-Ionic liquids (API-ILs) have the potential to improve the bioavailability of BCS Class IV Drugs. However, the problematic physical handling properties of room temperature API-ILs have impaired clinical and commercial exploitation to date. Lipid-based formulations (LBFs) are used to improve the absorption of drugs with limited bioavailability. Nonetheless, LBFs face limitations such as low drug loading capacity and sub-par physical stability. A platform for transforming API-ILs into solid forms at high loadings via spray encapsulation with polymers has been developed and previously demonstrated for hydrophilic API-ILs. The current work demonstrates that this platform technology can be applied to a lipophilic API-IL of the BCS Class IV API, chlorpromazine, and to multi-component solutions comprising API-IL and a LBF. Furthermore, solidification of a type IIIB, liquid LBF was achieved via spray encapsulation with cellulose- and methacrylate- based polymers for the first time. The spray-encapsulated formulations had excellent physical handling properties, and successfully eluted the API-IL in aqueous media. The chlorpromazine release profiles from the API-IL, the API-IL containing LBF, and the solidified formulations, were evaluated in vitro using phosphate buffer (pH 6.8) and fasted state simulated intestinal fluid (FaSSIF). Spray-encapsulated formulations exhibited improved release profiles compared to the liquid formulations. Overall, these findings indicate that phase-separated, polymeric, solid formulations of liquid API forms represent a promising platform technology for developing oral solid dosage forms of poorly bioavailable drugs.

Intestinal incision site infections: Evaluation of antimicrobial-coated vicryl sutures in preventing postoperative infections

This research focused on the development of an antimicrobial polymeric composite coating of polyethylene glycol (PEG) infused with zinc oxide nanoparticles (ZnO) and herbal extracts from Curcuma longa (turmeric). The synthesized composite is coated on a biodegradable vicryl suture via the dip coating method. Instrumental characterization, including Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), was utilized to confirm the chemical composition and surface of the coated suture. The antimicrobial activity was evaluated against bacterial pathogens, Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). The water contact angle was measured to determine surface wettability. Degradation studies were conducted in simulated intestinal fluid (SIF) to determine the coated suture’s longevity.

The development of functionalized alginate-based hydrogels for the management of postprandial hyperglycemia and weight reduction

Polysaccharide-derived functional food ingredients are increasingly prevalent in the food industry for their health benefits and functional versatility. Among them, sodium alginate (SA), a natural polysaccharide, is widely valued for its sustainability, renewability, non-toxic nature, and broad applicability. However, its poor water solubility has limited its use as biomedical materials and food additives. Here, we enhanced SA through carboxymethylation to produce carboxymethylated SA (CMSA), aiming to develop functional food ingredients with improved physicochemical properties for health management. The synthesized CMSA was characterized for its physical properties and ability to form a hydrogel through cross-linking with Ca2+. We assessed its encapsulation efficiency for food particles in simulated gastric and intestinal fluids and evaluated its physiological effects in a rat model. Our findings demonstrated that CMSA-based hydrogels effectively encapsulate ingredients in the stomach, reducing nutrient diffusion in the intestine, and helping to manage postprandial hypoglycemia. Additionally, the hydrogel expands in the stomach and small intestine, contributing to modest weight loss. These findings suggest that CMSA-based hydrogels offer significant potential as functional food ingredients for managing postprandial hypoglycemia and supporting weight management. The development of such gelling systems presents promising applications in both medical and nutritional sciences, offering innovative strategies for addressing diet-related health concerns.

Characterization and comparation of toxicity between natural realgar and artificially optimized realgar.

Realgar possesses important medical properties. This article aims to evaluate realgar and emerging artificially optimized realgar to ensure safe clinical use. Multiple techniques were employed to test natural realgar and artificially optimized realgar. Soluble arsenic content in representative samples were measured. Natural realgar and artificially optimized realgar were administered to KM mice via gavage for 28days, and the extent of liver and kidney tissue damage, arsenic accumulation and form of arsenic were measured. Natural realgar and artificially optimized realgar can be distinguished by their physical properties or spectral signatures. ICP-MS and EPMA identified different contents of elements between two groups. In simulated gastric and intestinal fluids, only As (III) and As (V) were detected. Toxicity experiments in vivo demonstrate that both groups caused minimal liver and kidney damage at a dose of 30mg·kg-1. At a dose of 180mg·kg-1, artificially optimized realgar caused significantly greater liver and kidney damage. The differences between natural realgar and artificially optimized realgar were successfully distinguished through several methods. In vitro experiments showed that As is the main component exerting their medicinal effects. In vivo toxicity tests demonstrated that at higher dose, artificially optimized realgar exhibited significantly higher toxicity, suggesting that natural and artificially optimized realgar have different toxic properties.

Differences in slow-release characteristics and release kinetics of three selenium nanoparticles from different synthesis strategies: Revealing the advantages synthesized by Lactiplantibacillus plantarum

The controlled release of selenium nanoparticles (SeNPs) is pivotal significance in improving bioavailability and mitigating potential side effects. Three types of SeNPs, Selenium nanoparticles synthesized by chemical method (CSeNPs), extracellular polysaccharide-encapsulated selenium nanoparticles (EPS-SeNP), and selenium nanoparticles synthesized by Lactiplantibacillus plantarum (LacSeNPs), were synthesized in this study using chemical reduction, polysaccharide-assisted, and microbial reduction methods, respectively. The selenium release kinetics of the nanoparticles were investigated in simulated gastrointestinal with five kinetics models. CSeNPs released 67.80% of selenium in simulated gastric fluids (SGF) and, depicting a Brownian motion fraction of 81.0. EPS-SeNPs released 77.38% of selenium in SGF while only releasing 16.28% in simulated intestinal fluids (SIF). The release process was primarily affected by changes in the nanoparticle structure after Super Case II Transport in SGF and the zero-order model in SIF. The zero-order model provided the best fit for releasing LacSeNP profiles in the SGF. In SIF, the release mechanism of LacSeNPs was regulated by combination of diffusion and carrier swelling or erosion, leading to non-Fickian diffusion. Therefore, synthetic nanoparticle methods determine their structures and compositions, leading to differences in their release kinetics and release mechanisms. Notably, the release of LacSeNPs in the SGF aligns with the absorption patterns of selenium within the human body. The current study elucidates the potential application advantages of SeNPs synthesized using microbial means as selenium-enriched supplements.

Probiotic and Postbiotic Potentials of Enterococcus faecalis EF-2001: A Safety Assessment.

Probiotics, which are live microorganisms that, when given in sufficient quantities, promote the host's health, have drawn a lot of interest for their ability to enhance gut health. Enterococcus faecalis, a member of the human gut microbiota, has shown promise as a probiotic candidate due to its functional attributes. However, safety concerns associated with certain strains warrant comprehensive evaluation before therapeutic application. In this study, E. faecalis EF-2001, originally isolated from fecal samples of a healthy human infant, was subjected to a multi-faceted assessment for its safety and probiotic potential. In silico analysis, CAZyme, biosynthetic, and stress-responsive proteins were identified. The genome lacked biogenic amine genes but contained some essential amino acid and vitamin synthetic genes, and carbohydrate-related enzymes essential for probiotic properties. The negligible difference of 0.03% between the 1st and 25th generations indicates that the genetic information of the E. faecalis EF-2001 genome remained stable. The live E. faecalis EF-2001 (E. faecalis EF-2001L) demonstrated low or no virulence potential, minimal D-Lactate production, and susceptibility to most antibiotics except some aminoglycosides. No bile salt deconjugation or biogenic amine production was observed in an in vitro assay. Hemolytic activity assessment showed a β-hemolytic pattern, indicating no red blood cell lysis. Furthermore, the EF-2001L did not produce gelatinase and tolerated simulated gastric and intestinal fluids in an in vitro study. Similarly, heat-killed E. faecalis EF-2001 (E. faecalis EF-2001HK) exhibits tolerance in both acid and base conditions in vitro. Further, no cytotoxicity of postbiotic EF-2001HK was observed in human colorectal adenocarcinoma HT-29 cells. These potential properties suggest that probiotic and postbiotic E. faecalis EF-2001 could be considered safe and retain metabolic activity suitable for human consumption.

Limited cellular uptake of liposomes: Might thiolated phospholipids hold the key?

AimIt was the aim of this study to evaluate the impact of surface thiolation on cellular uptake of liposomes. MethodsLiposomes were prepared via the thin lipid film method, incorporating cholesterol, dipalmitoylphosphatidylcholin (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol). The characterization of liposomes included size, polydispersity index, surface morphology, zeta potential and stability in simulated gastric and intestinal fluid. Hemocompatibility and cytotoxicity of liposomes were investigated. Cellular uptake studies were performed on Caco-2, HeLa, HEK and SW620 cells, involving both quantitative analysis through flow cytometry and qualitative evaluation via confocal microscopy. Additionally, we investigated the impact of an oxidizing agent on thiol-dependent uptake. ResultsNon-thiolated and thiolated liposomes exhibited a size of 149 nm to 274 nm and a PDI between 0.3 and 0.45. Liposomes were stable in simulated intestinal and gastric fluid. Hemocompatibility studies and cytocompatibility studies of liposomes showed negligible toxic effects of liposomes. Cellular uptake of thiolated liposomes was 1.8-, 2.1-, 5.4- and 1.4-fold enhanced in comparison to non-thiolated liposomes on Caco-2, HEK, HELA and SW620 cells, respectively. The results were qualitatively verified by confocal microscopy. Thiol dependent uptake was influenced by oxidizing agents on HeLa cells. ConclusionSurface thiolation represents a promising approach to enhance cellular uptake of liposomes.

FORMULATION OF SELF-NANO EMULSIFYING SYSTEM (SNES) CONTAINING SNAKEHEAD FISH EXTRACT PROTEIN INCORPORATED INTO CORN OIL BY HYDROPHOBIC ION PAIRING METHOD

Objective: The purpose of this study was to determine whether the protein complexation of snakehead fish extract using the hydrophobic ion pairing method with Sodium Dodecyl Sulfate (SDS) as a complexing ligand could be loaded into the corn oil component of the SNES and to explore the ratio of oil, surfactant, and cosurfactant in the Self-Nanoemulsifying System (SNES) formula that can produce good SNES characteristics. Methods: Snakehead fish proteins were extracted using pressurized hot water and then complexed with SDS at acidic pH. The SDS-protein complex was loaded into the oil component of the SNES and then combined with the surfactant component (Tween 80) and cosurfactant (propylene glycol) in a ratio of 1:9:1, which, based on the preliminary miscibility screening, has the best miscibility among other screening results. Results: The results of the study were as follows. The binding efficiency of the SDS-protein-complex was 31.74% and the loading efficiency into SNES was 83.17%. The nanoemulsion formed had visible light transmittance of 100.4%, particle size 72.7 nm, zeta potential-53.03 mV, and emulsification time 71.67 seconds. The nanoemulsion was stable at storage and 100 and 1000 times dilution challenges using aqueous media, Simulated Gastric Fluid (SGF), and Simulated Intestinal Fluid (SIF). Conclusion: The hydrophobic ion-pair complexation of snakehead fish protein extract with SDS as the complexing ligand was able to load the protein into the oil component of SNES and the ratio of oil, surfactant, and cosurfactant in the SNES formula that produce good SNES characteristics was corn oil, Tween 80, and propylene glycol at a ratio of 1:9:1

Development of a pH-Sensitive Nanoparticle via Self-Assembly of Fucoidan and Protamine for the Oral Delivery of Insulin.

Objectives: Oral insulin delivery has received much attention over the past 20 years due to its high compliance. The aim of this study is to prepare nanoparticles for the oral delivery of insulin; Methods: Fucoidan and protamine were used to prepare a pH-sensitive nanoparticle via self-assembly. The secondary structure and in vitro stability of the nanoparticles were characterized using FTIR, XRD, ITC, and TEM. the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. The pre-liminary therapeutic effect on high-fat-fed type 2 diabetic mice; Results: When the fucoidan/protamine mass ratio was 10:3 (w/w), the particle size and zeta potential were 140.83 ± 1.64 nm and -48.13 ± 0.61 mV.The encapsulation efficiency of insulin was 62.97 ± 0.59%. The preliminary therapeutic effect on type 2 diabetic mice showed that the fasting blood glucose of diabetic mice decreased from 10.28 ± 0.88 mmol/L to 9.22 ± 0.64 mmol/L, the area under the curve value of oral glucose tolerance test was reduced by 11.70%, and the insulin se-cretion of diabetic mice was increased by 13.3%; Conclusions: The nanoparticles were prepared successfully by self-assembly. The empty and insulin-loaded nanoparticles remained stable in simulated gastric fluid, and the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. Moreover, insulin-loaded nanoparticles could relieve on type 2 diabetic mice.

Studies on the Probiotic, Adhesion, and Induction Properties of Artisanal Lactic Acid Bacteria: to Customize a Gastrointestinal Niche to Trigger Anti-obesity Functions.

The primary goals of this work are to explore the potential of probiotic lactic acid bacteria's (LAB) mucin/mucus layer thickening properties and to identify anti-obesity candidate strains that improve appropriate habitat for use with the Akkermansia group population in the future. The HT-29 cell binding, antimicrobial properties, adhesion to the mucin/mucus layer, growth in the presence of mucin, stability during in vitro gastrointestinal (GI) conditions, biofilm formation, and mucin/mucus thickness increment abilities were all assessed for artisanal LAB strains. Sixteen LAB strains out of 40 were chosen for further analysis based on their ability to withstand GI conditions. Thirteen strains remained viable in simulated intestinal fluid, while most showed high viability in gastric juice simulation. Furthermore, 35.9-65.4% of those 16 bacteria adhered to the mucin layer. Besides, different lactate levels were produced, and Streptococcus thermophilus UIN9 exhibited the highest biofilm development. In the HT-29 cell culture, the highest mucin levels were 333.87µg/mL with O. AK8 at 50mM lactate, 313.38µg/mL with Lactobacillus acidophilus NRRL-B 1910 with initial mucin, and 311.41µg/mL with Lacticaseibacillus casei NRRL-B 441 with initial mucin and 50mM lactate. Nine LAB strains have been proposed as anti-obesity candidates, with olive isolates of Lactiplantibacillus plantarum being particularly important due to their ability to avoid mucin sugar consumption. Probiotic LAB's attachment to the colonic mucosa and its ability to stimulate HT-29 cells to secrete mucus are critical mechanisms that may support the development of Akkermansia.

A potential cocrystal strategy to tailor in-vitro dissolution and improve Caco-2 permeability and oral bioavailability of berberine

Berberine hydrochloride (BER), a promising candidate in treating tumors, diabetes and pain management, has relatively low oral absorption and bioavailability due to its low intestinal permeability. To address these challenges, we developed a BER and lornoxicam cocrystal (BLCC) by a solvent evaporation method and characterized it using X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Compared with BER, BLCC exhibited an instant release in pH 1.0 HCl and a sustained release up to 24 h in pH 6.8 buffer solutions and water. The Caco-2 permeability of BLCC has shown a remarkable increase compared to that of BER (i.e., Papp(a→b): 50.30 × 10-7vs 8.82 × 10-7 cm/s), which is attributed to the improved lipophilicity of BER (i.e., log P: 1.29 vs −1.83) and the reduced efflux amount of BER (i.e., ER: 1.71 vs 12.11). Furthermore, BLCC demonstrated a relative bioavailability of 410 % in comparison to the original BER, due to notably enhanced intestinal permeability of BLCC and its continuous dissolution in simulated intestinal fluid. BLCC has the potential to tailor the dissolution behavior, improve intestinal permeability, and boost the bioavailability of BER. This indicates that the cocrystal strategy holds promise as an effective approach to improving the oral absorption and bioavailability of active pharmaceutical molecules with low permeability during drug development.

Effect on heat treatment on the physical stability, interfacial tension and in vitro digestion of whey protein-stabilized ω-6/ω-3 fatty acid balanced pumpkin seed oil complex condensate

Despite the fact that whey proteins (WP) have shown diverse functional and nutritional properties, they exhibit poor stability when exposed to temperatures above the thermal denaturation point. Therefore, in this study, a complex coacervation layer of formed by WP treated at different heating temperatures (55, 65, 75 and 85 °C) and gum arabic (GA) was used as a wall material to microencapsulate ω-6/ω-3 fatty acid balanced pumpkin seed oil (MPO) with a view to exploring the effect of heat treatment temperatures on the nature of microencapsulation stabilized by WP-GA complexes. At pH 3.6, WP and GA formed a strong electrostatic complex. When the heat treatment temperature reached 65 °C, the WP-GA complexes exhibited more excellent particle size, absolute potential, emulsification properties and structural changes, which made them more suitable as hydrophilic emulsifiers to stabilize oil/water (O/W) systems. Further research into the physical properties and interfacial characteristics of O/W emulsions formed by the WP-GA complex was conducted. When subjected to a heat treatment temperature of 65 °C, the O/W emulsions achieved a higher interfacial protein content (3.17 ± 0.08 mg/m2), along with a lower interfacial tension (15.52 mN/m). Additionally, the encapsulated MPO demonstrates superior oxidative stability compared to its unencapsulated counterpart. In-vitro simulated digestion experiments revealed that only small fraction (17.70 ± 1.13%) of the encapsulated oil was released in simulated gastric fluid, while the majority (76.70 ± 1.47%) was released in simulated intestinal fluid, which suggested that the WP-GA composite coacervates was a promising encapsulation shell material, capable of maintaining integrity in the gastric phase and effectively delivering the encapsulant to the intestinal phase.

Multifunctional nanoplatforms based on alumina-coated mesoporous silica with potential for cancer theranostics applications

Multifunctional nanoplatforms based on mesoporous silica coated with alumina were successfully and sustainably synthesized using sodium silicate extracted from rice husk ash (RHA), demonstrating the potential for cancer theranostics. The hybrid nanostructures produced (C2-600 and C4-600), from two different calcination times, exhibited distinct morphologies, textural parameters, and degrees of mesoscopic organization. As expected, the Al2O3 coating on the mesoporous silica nanoparticles (MSNs) reduced the specific surface area from 720 m2/g to 122 m2/g (C2-600) and 57 m2/g (C4-600), while preserving their mesoporous structure. Additionally, both C2-600 and C4-600 showed relatively good stability across a wide pH interval, with a zeta potential of ζ = -15 mV and hydrodynamic diameter (Dh) ranging from 160 to 670 nm, depending on the pH of the medium. These peculiar characteristics resulted in high encapsulation efficiency (EE ≈ 90%) for the doxorubicin (DOX) anticancer drug, as well as sustained drug release in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). Appreciably, C4-600-DOX released approximately 83% of the drug over 96 hours and demonstrated significant biodegradation in simulated biological media. Furthermore, the hybrid nanoplatforms exhibited strong optical absorption between 250 and 420 nm, along with broad and intense photoluminescence (PL) in the near-infrared (NIR) region (680-900 nm), which is highly desirable for NIR-fluorescence diagnostic imaging. Notably, the hybrid nanoplatforms without DOX were non-cytotoxic to fibroblast and Caco-2 cells, while the DOX-loaded nanoplatforms exhibited selectivity and potent anticancer activity, inhibiting approximately 80% of Caco-2 colorectal cancer cells after 72 hours. These findings demonstrate that C2-600 and C4-600 are innovative, multifunctional and biodegradable nanoplatforms with powerful potential as drug carriers and fluorescence imaging agents, making them promising candidates for cancer theranostics.

Preparation, Characterization and in Vitro Stability of Soy Protein Fibrils Ferrous Delivery System

Iron deficiency is considered widespread globally, and discovering ferrous ion delivery system with better stability is one of the keys to solving this problem. In this paper, a ferrous ion delivery system was prepared from soy isolate protein fibrils (SPNFs). The alterations in infrared spectrum and microstructure before and after loading were compared, and the ionic strength stability, freeze-thaw stability, and oxidative reaction activity of soy isolate protein fibrils loaded with ferrous iron (SPNFs-Fe) were analyzed, simulating the release kinetics of gastrointestinal digestion. The results demonstrated that SPNFs load ferrous ions with carboxyl, carbonyl, and amino groups. SPNFs-Fe had good ionic strength stability and excellent freeze-thaw stability and showed weak pro-oxidation activity. The release kinetics of SPNFs-Fe in simulated gastrointestinal digestion best fit the Ritger-Peppas model, which had a slow-release effect in simulated gastrointestinal digestion. The release of SPNFs-Fe in simulated gastric fluid belonged to Fick diffusion, while in simulated intestinal fluid it belonged to non-Fick diffusion. These results suggest that SPNFs-Fe is a promising ferrous delivery system as a supplementary source of iron.

Bionic cell wall models: Utilizing TEMPO-oxidized cellulose nanofibers for fucoxanthin delivery systems

Fucoxanthin (FX) has various excellent biological properties but suffers from poor bioavailability. In this work, we build a bionic cell wall model using TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-oxidized cellulose. The bionic cell wall enhances the environmental stability of the liposomes and serves as a pH-responsive mechanism. The coating processes protect the structure of liposomes and fucoxanthin under the acidic conditions of the stomach. The bionic cell wall dispersed and released the fucoxanthin in simulated intestinal fluid. Overall, the protective and release capabilities highlight the potential of cellulose in a bionic cell wall model and provide diversity for the structural design of carriers for delivering functional bioactive components.

3D printing novel enteric capsule shells for personalized drug delivery

Individualized drug delivery presents a viable strategy for enhancing medication efficacy and patient safety. It involves producing small batches of custom dosages tailored to each patient’s individual needs. However, current pharmaceutical manufacturing processes are not designed for personalized dosage forms. Additive manufacturing processes have great potential in the pharmaceutical industry due to the customizable nature of 3D printing technologies and the increasing demand for customized pharmaceutics and drug delivery systems. Conventional enteric capsules are prepared by dip coating to achieve gastro-resistant release, but the manufacturing process is erratic and unreliable. This study aimed to investigate the feasibility of manufacturing enteric capsules from enteric polymers using the hot melt extrusion (HME) and fused filament fabrication (FFF) process. HME was utilized to prepare filaments using enteric polymers, Hypromellose acetate succinate (HPMC-AS), and Eudragit-L 100–55, with plasticizers, sorbitol, and polyethylene glycol 4000 (PEG-4000), and a thermoplastic polymer, polyvinyl alcohol (PVA). A computer-aided design program was utilized to design size 0 capsules. The prepared capsule design and filaments were used to fabricate capsules using the FFF process. Powdered red dye was used to simulate the drug and its release from FFF fabricated capsules was evaluated in simulated gastric and intestinal fluids, pH 1.2 and 6.8, respectively. Various combinations of enteric polymer, plasticizer, and thermoplastic polymer were examined. Thermogravimetric analysis (TGA) showed that the temperatures used for processing polymer blends were well below their thermal degradation temperatures, and dye release profiles were generated using image analysis software. This study demonstrates that capsules made with HPMCAS, PEG-4000, and PVA via the FFF process are suitable for controlling drug release and that the release profile can be modified by making small changes to the formulation.

Alginate sulfonamide hydrogel beads for 5-fluorouracil delivery: antitumor activity, cytotoxicity assessment, and theoretical investigation

This study focused on grafting a new monomer (E)-N-(4-(3-(4-bromophenyl) acryloyl) phenyl)-4-methyl benzene sulfonamide (Br-PS) onto sodium alginate (Alg) using a free radical polymerization method. The optimal parameters for the grafting polymerization reaction were investigated, including initiator and monomer concentrations, polymerization reaction duration, and temperature. Additionally, the conversion, graft, and solid content percentages were calculated. The resulting novel poly (Br-PS)-g-Alg was thoroughly analyzed using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Moreover, poly (Br-PS)-g-Alg was tested for cytotoxicity and selectivity values on lung cancer cell line (A549), breast cancer cell line (MDA-MB-231), and a normal cell line (MDCK) using the neutral red uptake test. Poly (Br-PS)-g-Alg demonstrated more inhibitory impact (IC50 = 33.37 and 40.9 μg/mL) and high selectivity (selectivity index = 4.83 and 3.94) on the A549 and MDA-MB-231 cell lines, respectively. Furthermore, uniform beads of creative poly (Br-PS)-g-Alg were fabricated, and their swelling rate in various media was studied. These beads could potentially serve as drug carriers for 5-fluorouracil (5-FU). Release experiments in simulated gastric (SGF) and intestinal fluids (SIF) showed a slower 5-FU release pattern in SGF compared to SIF. The proposed structures of poly (Br-PS)-g-Alg were theoretically verified using density functional theory with DFT/B3LYP/6–31(G) basis set, revealing distinct interactions due to the presence of different functional groups. The findings of this study could significantly impact the development of new drug delivery systems.