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1.
J Nanobiotechnology ; 22(1): 287, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797862

ABSTRACT

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment's impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel's synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.


Subject(s)
Bone Regeneration , Chitosan , Drug Delivery Systems , Hydrogels , Metal-Organic Frameworks , Periodontitis , Periodontitis/drug therapy , Hydrogels/chemistry , Bone Regeneration/drug effects , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Chitosan/chemistry , Chitosan/analogs & derivatives , Mice , Drug Delivery Systems/methods , Dextrans/chemistry , Male , Reactive Oxygen Species/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Delayed-Action Preparations/chemistry , Humans
2.
Int J Biol Macromol ; 269(Pt 2): 132132, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723831

ABSTRACT

Sustainable release of drug by utilizing ß-cyclodextrin (ß-CD) based inclusion complex (IC) is the prime objective of the present work. Herein, polyacrylamide/dextran containing carbon quantum dots (PAM/Dex/CQD) nanocomposite hydrogels are prepared by in situ polymerization of acrylamide. The incorporation of CQD triggers the change in orientation of the PAM/Dex polymeric chains to result the formation of stacked surface morphology of the hydrogel. The average particle size of CQD is found to be 4.13 nm from HRTEM analysis. As-synthesized nanocomposite hydrogel exhibits an optimum swelling ratio of 863 % in aqueous medium. The cytotoxicity study is conducted on HeLa cells by taking up to 2 µM concentration of the prepared nanocomposite hydrogel demonstrate 78 % cell viability. In present study, ciprofloxacin (Cipro) is taken as model drug that achieves release of 64.15 % in 32 h from ß-Cipro@PAM/Dex/CQD hydrogels in acidic medium. From theoretical study, release rate constants, R2, Akaike information criterion (AIC) and model selection criterion (MSC) are computed to determine the best fitted kinetics model. Peppas-Sahlin model is the best fitted kinetics model for ß-Cipro@PAM/Dex/CQD and concluded that the release of Cipro follows Fickian drug diffusion mechanism in acidic medium.


Subject(s)
Acrylic Resins , Carbon , Ciprofloxacin , Dextrans , Drug Liberation , Hydrogels , Quantum Dots , Ciprofloxacin/chemistry , Quantum Dots/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Acrylic Resins/chemistry , Dextrans/chemistry , Kinetics , Humans , Carbon/chemistry , Drug Carriers/chemistry , HeLa Cells
3.
Int J Biol Macromol ; 270(Pt 2): 132409, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768918

ABSTRACT

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.


Subject(s)
Biocompatible Materials , Chitosan , Regeneration , Tissue Adhesives , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacology , Animals , Regeneration/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Materials Testing , Meniscus/drug effects , Dextrans/chemistry , Cell Survival/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Rabbits , Tibial Meniscus Injuries/surgery , Humans , Injections
4.
Carbohydr Polym ; 337: 122147, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710554

ABSTRACT

Treatment of infected wound by simultaneously eliminating bacteria and inducing angiogenesis to promote wound tissue regeneration remains a clinical challenge. Dynamic and reversable hydrogels can adapt to irregular wound beds, which have raised great attention as wound dressings. Herein, a sprayable chitosan-based hydrogel (HPC/CCS/ODex-IGF1) was developed using hydroxypropyl chitosan (HPC), caffeic acid functionalized chitosan (CCS), oxidized dextran (ODex) to crosslink through the dynamic imine bond, which was pH-responsive to the acidic microenvironment and could controllably release insulin growth factor-1 (IGF1). The HPC/CCS/ODex-IGF1 hydrogels not only showed self-healing, self-adaptable and sprayable properties, but also exhibited excellent antibacterial ability, antioxidant property, low-cytotoxicity and angiogenetic activity. In vivo experiments demonstrated that hydrogels promoted tissue regeneration and healing of bacteria-infected wound with a rate of approximately 98.4 % on day 11 by eliminating bacteria, reducing inflammatory and facilitating angiogenesis, demonstrating its great potential for wound dressing.


Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Neovascularization, Physiologic , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Neovascularization, Physiologic/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Humans , Male , Insulin-Like Growth Factor I , Staphylococcus aureus/drug effects , Bandages , Wound Infection/drug therapy , Wound Infection/microbiology , Dextrans/chemistry , Dextrans/pharmacology , Angiogenesis
5.
Nutrients ; 16(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732595

ABSTRACT

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.


Subject(s)
Colitis , Colon , Dextran Sulfate , Diet, Ketogenic , Dietary Fats , Disease Models, Animal , Fluorescein-5-isothiocyanate/analogs & derivatives , Mice, Inbred C57BL , Animals , Colitis/chemically induced , Colitis/diet therapy , Male , Mice , Dietary Fats/adverse effects , Colon/pathology , Colon/metabolism , Permeability , Tight Junction Proteins/metabolism , Interleukin-1beta/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Tumor Necrosis Factor-alpha/metabolism , Fatty Acids , Dextrans
6.
Biomacromolecules ; 25(5): 3122-3130, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38696355

ABSTRACT

Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (D < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.


Subject(s)
Dextrans , Peptides , Polymerization , Dextrans/chemistry , Peptides/chemistry , Peptides/chemical synthesis , Polymers/chemistry , Polymers/chemical synthesis , Cyclic N-Oxides/chemistry , Anhydrides/chemistry , Polysaccharides/chemistry , Micelles
7.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763712

ABSTRACT

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.


Subject(s)
Cell Adhesion , Chitosan , Dextrans , Hydrogels , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Dextrans/chemistry , Humans , Cell Adhesion/drug effects , Cell Survival/drug effects , Collagen/chemistry , Animals , Drug Liberation , Cell Proliferation/drug effects , Cell Encapsulation/methods , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Mice , Biomimetics/methods , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Scaffolds/chemistry
8.
Fr J Urol ; 34(2): 102585, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38717460

ABSTRACT

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.


Subject(s)
Dextrans , Hyaluronic Acid , Ureteral Obstruction , Vesico-Ureteral Reflux , Humans , Vesico-Ureteral Reflux/therapy , Retrospective Studies , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/therapeutic use , Hyaluronic Acid/adverse effects , Female , Male , Dextrans/therapeutic use , Dextrans/administration & dosage , Dextrans/adverse effects , Child, Preschool , Treatment Outcome , Infant , Acrylic Resins/therapeutic use , Acrylic Resins/administration & dosage , Child , Injections , Cohort Studies , Ureteroscopy/adverse effects
9.
Transl Vis Sci Technol ; 13(5): 5, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38713474

ABSTRACT

Purpose: The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS-BRB modulation can offer a novel method for targeted retinal therapy. Methods: AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure. Results: FUS-BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage. Conclusions: This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases. Translational Relevance: Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.


Subject(s)
Blood-Retinal Barrier , Gold , Metal Nanoparticles , Retinal Ganglion Cells , Animals , Gold/chemistry , Gold/administration & dosage , Retinal Ganglion Cells/cytology , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Dextrans/administration & dosage , Dextrans/chemistry , Drug Delivery Systems/methods , Rats , Microscopy, Confocal/methods , Male
10.
Int J Biol Macromol ; 269(Pt 2): 131851, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692543

ABSTRACT

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.


Subject(s)
Dextrans , Hydrogels , Phosphates , Water Pollutants, Chemical , Water Purification , Adsorption , Dextrans/chemistry , Porosity , Phosphates/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Kinetics , Water Purification/methods , Hydrogels/chemistry , Thermodynamics , Hydrogen-Ion Concentration , Solutions , Water/chemistry
11.
J Mater Chem B ; 12(21): 5248-5260, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38712662

ABSTRACT

Intracellular bacteria are considered to play a key role in the failure of bacterial infection therapy and increase of antibiotic resistance. Nanotechnology-based drug delivery carriers have been receiving increasing attention for improving the intracellular antibacterial activity of antibiotics, but are accompanied by disadvantages such as complex preparation procedures, lack of active targeting, and monotherapy, necessitating further design improvements. Herein, nanoparticles targeting bacteria-infected macrophages are fabricated to eliminate intracellular bacterial infections via antibiotic release and upregulation of intracellular reactive oxygen species (ROS) levels and proinflammatory responses. These nanoparticles were formed through the reaction of the amino group on selenocystamine dihydrochloride and the aldehyde group on oxidized dextran (ox-Dex), which encapsulates vancomycin (Van) through hydrophobic interactions. These nanoparticles could undergo targeted uptake by macrophages via endocytosis and respond to the bacteria-infected intracellular microenvironment (ROS and glutathione (GSH)) for controlled release of antibiotics. Furthermore, these nanoparticles could consume intracellular GSH and promote a significant increase in the level of ROS in macrophages, subsequently up-regulating the proinflammatory response to reinforce antibacterial activity. These nanoparticles can accelerate bacteria-infected wound healing. In this work, nanoparticles were fabricated for bacteria-infected macrophage-targeted and microenvironment-responsive antibiotic delivery, cellular ROS generation, and proinflammatory up-regulation activity to eliminate intracellular bacteria, which opens up a new possibility for multifunctional drug delivery against intracellular infection.


Subject(s)
Anti-Bacterial Agents , Immunotherapy , Macrophages , Nanoparticles , Reactive Oxygen Species , Nanoparticles/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Animals , Mice , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Dextrans/chemistry , Dextrans/pharmacology , Vancomycin/pharmacology , Vancomycin/chemistry , Bacterial Infections/drug therapy , Microbial Sensitivity Tests , Cystamine/chemistry , Cystamine/pharmacology , Staphylococcus aureus/drug effects , Drug Carriers/chemistry , Particle Size
12.
ACS Nano ; 18(22): 14145-14160, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38761153

ABSTRACT

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.


Subject(s)
Dendrimers , Doxorubicin , Glioblastoma , Matrix Metalloproteinases , Nanoparticles , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/metabolism , Doxorubicin/pharmacology , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Hydrogen-Ion Concentration , Animals , Nanoparticles/chemistry , Humans , Mice , Dendrimers/chemistry , Matrix Metalloproteinases/metabolism , Dextrans/chemistry , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Cell Line, Tumor , Drug Delivery Systems , Tumor Microenvironment/drug effects , Drug Carriers/chemistry , Mice, Nude
13.
Nutrients ; 16(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38612988

ABSTRACT

The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli. Recent evidence suggests that the milk fat globule membrane (MFGM) and its milk phospholipid component (MPL) can benefit the GIT through improving barrier function. Our objective was to compare the effects of two digested MFGM ingredients with or without dextran sodium sulfate (DSS)-induced barrier stress on mucin proteins. Co-cultured Caco-2/HT29-MTX intestinal cells were treated with in vitro digests of 2%, 5%, and 10% (w/v) MFGM or MPL alone for 6 h or followed by challenge with 2.5% DSS (6 h). Transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran (FD4) permeability measurements were used to measure changes in barrier integrity. Mucin characterization was performed using a combination of slot blotting techniques for secreted (MUC5AC, MUC2) and transmembrane (MUC3A, MUC1) mucins, scanning electron microscopy (SEM), and periodic acid Schiff (PAS)/Alcian blue staining. Digested MFGM and MPL prevented a DSS-induced reduction in secreted mucins, which corresponded to the prevention of DSS-induced increases in FD4 permeability. SEM and PAS/Alcian blue staining showed similar visual trends for secreted mucin production. A predictive bioinformatic approach was also used to identify potential KEGG pathways involved in MFGM-mediated mucosal maintenance under colitis conditions. This preliminary in silico evidence, combined with our in vitro findings, suggests the role of MFGM in inducing repair and maintenance of the mucosal barrier.


Subject(s)
Dextrans , Fluorescein-5-isothiocyanate/analogs & derivatives , Glycolipids , Glycoproteins , Lipid Droplets , Humans , Caco-2 Cells , Alcian Blue , Glycoproteins/pharmacology , Epithelial Cells , Mucins
14.
PLoS One ; 19(4): e0297738, 2024.
Article in English | MEDLINE | ID: mdl-38626108

ABSTRACT

The nucleus preserves the genomic DNA of eukaryotic organisms and maintains the integrity of the cell by regulating the transport of molecules across the nuclear membrane. It is hitherto assumed that small molecules having a size below the passive permeability limit are allowed to diffuse freely to the nucleus while the transport of larger molecules is regulated via an active mechanism involving energy. Here we report on the kinetics of nuclear import and export of dextran molecules having a size below the passive permeability limit. The studies carried out using time-lapse confocal fluorescence microscopy show a clear deviation from the passive diffusion model. In particular, it is observed that the steady-state concentration of dextran molecules inside the nucleus is consistently less than the concentration outside, in contradiction to the predictions of the passive diffusion model. Detailed analysis and modeling of the transport show that the nuclear export rates significantly differ from the import rates, and the difference in rates is dependent on the size of the molecules. The nuclear export rates are further confirmed by an independent experimental study where we observe the diffusion of dextran molecules from the nucleus directly. Our experiments and transport model would suggest that the nucleus actively rejects exogenous macromolecules even below the passive permeability limit. This result can have a significant impact on biomedical research, especially in areas related to targeted drug delivery and gene therapy.


Subject(s)
Cell Nucleus , Nuclear Envelope , Nuclear Envelope/metabolism , Cell Nucleus/metabolism , Dextrans/metabolism , Active Transport, Cell Nucleus , Diffusion
15.
PLoS One ; 19(4): e0301432, 2024.
Article in English | MEDLINE | ID: mdl-38626169

ABSTRACT

Diffusion within extracellular matrix is essential to deliver nutrients and larger metabolites to the avascular region of the meniscus. It is well known that both structure and composition of the meniscus vary across its regions; therefore, it is crucial to fully understand how the heterogenous meniscal architecture affects its diffusive properties. The objective of this study was to investigate the effect of meniscal region (core tissue, femoral, and tibial surface layers) and molecular weight on the diffusivity of several molecules in porcine meniscus. Tissue samples were harvested from the central area of porcine lateral menisci. Diffusivity of fluorescein (MW 332 Da) and three fluorescence-labeled dextrans (MW 3k, 40k, and 150k Da) was measured via fluorescence recovery after photobleaching. Diffusivity was affected by molecular size, decreasing as the Stokes' radius of the solute increased. There was no significant effect of meniscal region on diffusivity for fluorescein, 3k and 40k dextrans (p>0.05). However, region did significantly affect the diffusivity of 150k Dextran, with that in the tibial surface layer being larger than in the core region (p = 0.001). Our findings contribute novel knowledge concerning the transport properties of the meniscus fibrocartilage. This data can be used to advance the understanding of tissue pathophysiology and explore effective approaches for tissue restoration.


Subject(s)
Dextrans , Meniscus , Animals , Swine , Dextrans/metabolism , Meniscus/metabolism , Menisci, Tibial/physiology , Fibrocartilage/metabolism , Fluoresceins/metabolism
16.
Methods Mol Biol ; 2788: 49-66, 2024.
Article in English | MEDLINE | ID: mdl-38656508

ABSTRACT

Calibrated size exclusion chromatography (SEC) is a useful tool for the analysis of molecular dimensions of polysaccharides. The calibration takes place with a set of narrow distributed dextran standards and peak position technique. Adapted columns systems and dissolving processes enable for the adequate separation of carbohydrate polymers. Plant-extracted fructan (a homopolymer with low molar mass and excellent water solubility) and mucilage (differently structured, high molar mass heteropolysaccarides that include existing supramolecular structures, and require a long dissolving time) are presented as examples of the versatility of this technique. Since narrow standards similar to the samples (chemically and structurally) are often unavailable, it must be noted that the obtained molar mass values and distributions by this method are only apparent (relative) values, expressed as dextran equivalents.


Subject(s)
Chromatography, Gel , Molecular Weight , Polysaccharides , Chromatography, Gel/methods , Polysaccharides/chemistry , Polysaccharides/analysis , Dextrans/chemistry , Fructans/chemistry , Fructans/analysis , Calibration
17.
Food Chem ; 449: 139310, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38608612

ABSTRACT

This study investigated the effects of the conjugate reaction sequences of whey protein concentrate (WPC), epigallocatechin gallate (EGCG) and dextran (DEX) on the structure and emulsion properties of conjugates and the bioaccessibility of astaxanthin (AST). Two types of ternary covalent complexes were synthesised using WPC, EGCG and DEX, which were regarded as emulsifiers of AST nanoemulsions. Results indicated that the WPC-DEX-EGCG conjugate (referred to as 'con') exhibits a darker SDS-PAGE dispersion band and higher contents of α-helix (6%), ß-angle (24%) and random coil (32%), resulting in a greater degree of unfolding structure and fluorescence quenching. These findings suggested WPC-DEX-EGCG con had the potential to exhibit better emulsification properties than WPC-EGCG-DEX con. AST encapsulation efficiency (76.22%) and bioavailability (31.89%) also demonstrated the superior performance of the WPC-DEX-EGCG con emulsifier in nanoemulsion delivery systems. These findings indicate that altering reaction sequences changes protein conformation, enhancing the emulsification properties and bioavailability of AST.


Subject(s)
Biological Availability , Catechin/analogs & derivatives , Emulsifying Agents , Emulsions , Whey Proteins , Xanthophylls , Xanthophylls/chemistry , Emulsions/chemistry , Emulsifying Agents/chemistry , Whey Proteins/chemistry , Animals , Catechin/chemistry , Dextrans/chemistry , Male , Rats , Rats, Sprague-Dawley
18.
Langmuir ; 40(17): 9082-9096, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38619979

ABSTRACT

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria), as well as MRSA bacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSA and significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.


Subject(s)
Anti-Bacterial Agents , Chitosan , Escherichia coli , Hydrogels , Methicillin-Resistant Staphylococcus aureus , Wound Healing , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Animals , Chitosan/chemistry , Chitosan/pharmacology , Dextrans/chemistry , Dextrans/pharmacology , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Mice , Polysaccharides/chemistry , Polysaccharides/pharmacology
19.
Molecules ; 29(8)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38675647

ABSTRACT

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.


Subject(s)
Contrast Media , Magnetic Iron Oxide Nanoparticles , Magnetic Resonance Imaging , Magnetite Nanoparticles , Theranostic Nanomedicine , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Resonance Imaging/methods , Contrast Media/chemistry , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Humans , Gold/chemistry , Dextrans/chemistry , Gadolinium/chemistry , Surface Properties , Hyperthermia, Induced/methods , Particle Size
20.
Biomater Sci ; 12(11): 2943-2950, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38651530

ABSTRACT

The widespread use of video-assisted thoracoscopic surgery (VATS) has triggered the rapid expansion in the field of computed tomography (CT)-guided preoperative localization and near-infrared (NIR) fluorescence image-guided surgery. However, its broader application has been hindered by the absence of ideal imaging contrasts that are biocompatible, minimally invasive, highly resolvable, and perfectly localized within the diseased tissue. To achieve this goal, we synthesize a dextran-based fluorescent and iodinated hydrogel, which can be injected into the tissue and imaged with both CT and NIR fluorescence modalities. By finely tuning the physical parameters such as gelation time and composition of iodinated oil (X-ray contrast agent) and indocyanine green (ICG, NIR fluorescence dye), we optimize the hydrogel for prolonged localization at the injected site without losing the dual-imaging capability. We validate the effectiveness of the developed injectable dual-imaging platform by performing image-guided resection of pulmonary nodules on tumor-bearing rabbits, which are preoperatively localized with the hydrogel. The injectable dual-imaging marker, therefore, can emerge as a powerful tool for surgical guidance.


Subject(s)
Fluorescent Dyes , Hydrogels , Indocyanine Green , Hydrogels/chemistry , Hydrogels/administration & dosage , Animals , Indocyanine Green/administration & dosage , Indocyanine Green/chemistry , Rabbits , Fluorescent Dyes/chemistry , Fluorescent Dyes/administration & dosage , Surgery, Computer-Assisted , Optical Imaging , Tomography, X-Ray Computed , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Dextrans/chemistry , Dextrans/administration & dosage , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Injections , Humans
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