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1.
Fr J Urol ; 34(2): 102585, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38717460

RESUMO

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.


Assuntos
Dextranos , Ácido Hialurônico , Obstrução Ureteral , Refluxo Vesicoureteral , Humanos , Refluxo Vesicoureteral/terapia , Estudos Retrospectivos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Ácido Hialurônico/efeitos adversos , Feminino , Masculino , Dextranos/uso terapêutico , Dextranos/administração & dosagem , Dextranos/efeitos adversos , Pré-Escolar , Resultado do Tratamento , Lactente , Resinas Acrílicas/uso terapêutico , Resinas Acrílicas/administração & dosagem , Criança , Injeções , Estudos de Coortes , Ureteroscopia/efeitos adversos
2.
Biomacromolecules ; 25(5): 3122-3130, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38696355

RESUMO

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.


Assuntos
Dextranos , Peptídeos , Polimerização , Dextranos/química , Peptídeos/química , Peptídeos/síntese química , Polímeros/química , Polímeros/síntese química , Óxidos N-Cíclicos/química , Anidridos/química , Polissacarídeos/química , Micelas
3.
Nutrients ; 16(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732595

RESUMO

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.


Assuntos
Colite , Colo , Sulfato de Dextrana , Dieta Cetogênica , Gorduras na Dieta , Modelos Animais de Doenças , Fluoresceína-5-Isotiocianato/análogos & derivados , Camundongos Endogâmicos C57BL , Animais , Colite/induzido quimicamente , Colite/dietoterapia , Masculino , Camundongos , Gorduras na Dieta/efeitos adversos , Colo/patologia , Colo/metabolismo , Permeabilidade , Proteínas de Junções Íntimas/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácidos Graxos , Dextranos
4.
J Nanobiotechnology ; 22(1): 287, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797862

RESUMO

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.


Assuntos
Regeneração Óssea , Quitosana , Sistemas de Liberação de Medicamentos , Hidrogéis , Estruturas Metalorgânicas , Periodontite , Periodontite/tratamento farmacológico , Hidrogéis/química , Regeneração Óssea/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Animais , Quitosana/química , Quitosana/análogos & derivados , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Dextranos/química , Masculino , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Preparações de Ação Retardada/química , Humanos
5.
Int J Biol Macromol ; 269(Pt 2): 131851, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692543

RESUMO

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.


Assuntos
Dextranos , Hidrogéis , Fosfatos , Poluentes Químicos da Água , Purificação da Água , Adsorção , Dextranos/química , Porosidade , Fosfatos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Cinética , Purificação da Água/métodos , Hidrogéis/química , Termodinâmica , Concentração de Íons de Hidrogênio , Soluções , Água/química
6.
J Mater Chem B ; 12(21): 5248-5260, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38712662

RESUMO

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.


Assuntos
Antibacterianos , Imunoterapia , Macrófagos , Nanopartículas , Espécies Reativas de Oxigênio , Nanopartículas/química , Antibacterianos/química , Antibacterianos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Dextranos/química , Dextranos/farmacologia , Vancomicina/farmacologia , Vancomicina/química , Infecções Bacterianas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Cistamina/química , Cistamina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula
7.
Int J Biol Macromol ; 269(Pt 2): 132132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723831

RESUMO

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.


Assuntos
Resinas Acrílicas , Carbono , Ciprofloxacina , Dextranos , Liberação Controlada de Fármacos , Hidrogéis , Pontos Quânticos , Ciprofloxacina/química , Pontos Quânticos/química , Hidrogéis/química , Hidrogéis/síntese química , Resinas Acrílicas/química , Dextranos/química , Cinética , Humanos , Carbono/química , Portadores de Fármacos/química , Células HeLa
8.
J Phys Chem B ; 128(22): 5293-5309, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38808573

RESUMO

Given the fact that the cellular interior is crowded by many different kinds of macromolecules, it is important that in vitro studies be carried out in the presence of mixed crowder systems. In this regard, we have used binary crowders formed by the combination of some of the commonly used crowding agents, namely, Ficoll 70, Dextran 70, Dextran 40, and PEG 8000 (PEG 8), to study how these affect enzyme activity, dynamics, and crowder diffusion. The enzyme chosen is AK3L1, an isoform of adenylate kinase. To investigate its dynamics, we have carried out three single point mutations (A74C, A132C, and A209C) with the cysteine residues being labeled with a coumarin-based solvatochromic probe [CPM: (7-diethylamino-3-(4-maleimido-phenyl)-4-methylcoumarin)]. Both enzyme activity and dynamics decreased in the binary mixtures as compared with the sum of the individual crowders, suggesting a reduction in excluded volume (in the mixture). To gain deeper insights into the binary mixtures, fluorescence correlation spectroscopy studies were carried out using fluorescein isothiocyanate-labeled Dextran 70 and tetramethylrhodamine-labeled AK3L1 as the diffusion probes. Diffusion in binary mixtures was observed to be much more constrained (relative to the sum of the individual crowders) for the labeled enzyme as compared to the labeled crowder showing different environments being faced by the two species. This was further confirmed during imaging of the phase-separated droplets formed in the binary mixtures having PEG as one of the crowding agents. The interior of these droplets was found to be rich in crowders and densely packed, as shown by confocal and digital holographic microscopy images, with the enzymes predominantly residing outside these droplets, that is, in the relatively less crowded regions. Taken together, our data provide important insights into various aspects of the simplest form of mixed crowding, that is, composed of just two components, and also hint at the enhanced complexity that the cellular interior presents toward having a detailed and comprehensive understanding of the same.


Assuntos
Adenilato Quinase , Polietilenoglicóis , Difusão , Adenilato Quinase/metabolismo , Adenilato Quinase/química , Adenilato Quinase/genética , Polietilenoglicóis/química , Ficoll/química , Dextranos/química , Dextranos/metabolismo , Espectrometria de Fluorescência , Mutação Puntual , Cumarínicos/química , Cumarínicos/metabolismo
9.
ACS Nano ; 18(22): 14145-14160, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38761153

RESUMO

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.


Assuntos
Dendrímeros , Doxorrubicina , Glioblastoma , Metaloproteinases da Matriz , Nanopartículas , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Concentração de Íons de Hidrogênio , Animais , Nanopartículas/química , Humanos , Camundongos , Dendrímeros/química , Metaloproteinases da Matriz/metabolismo , Dextranos/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Microambiente Tumoral/efeitos dos fármacos , Portadores de Fármacos/química , Camundongos Nus
10.
Int J Biol Macromol ; 270(Pt 2): 132409, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768918

RESUMO

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.


Assuntos
Materiais Biocompatíveis , Quitosana , Regeneração , Adesivos Teciduais , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Animais , Regeneração/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Quitosana/farmacologia , Teste de Materiais , Menisco/efeitos dos fármacos , Dextranos/química , Sobrevivência Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Coelhos , Lesões do Menisco Tibial/cirurgia , Humanos , Injeções
11.
Carbohydr Polym ; 337: 122147, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710554

RESUMO

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.


Assuntos
Antibacterianos , Quitosana , Hidrogéis , Neovascularização Fisiológica , Cicatrização , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Humanos , Masculino , Fator de Crescimento Insulin-Like I , Staphylococcus aureus/efeitos dos fármacos , Bandagens , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Dextranos/química , Dextranos/farmacologia , Angiogênese
12.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763712

RESUMO

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.


Assuntos
Adesão Celular , Quitosana , Dextranos , Hidrogéis , Hidrogéis/química , Hidrogéis/farmacologia , Quitosana/química , Dextranos/química , Humanos , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Animais , Liberação Controlada de Fármacos , Proliferação de Células/efeitos dos fármacos , Encapsulamento de Células/métodos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos , Biomimética/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais/química
13.
Transl Vis Sci Technol ; 13(5): 5, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713474

RESUMO

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.


Assuntos
Barreira Hematorretiniana , Ouro , Nanopartículas Metálicas , Células Ganglionares da Retina , Animais , Ouro/química , Ouro/administração & dosagem , Células Ganglionares da Retina/citologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Dextranos/administração & dosagem , Dextranos/química , Sistemas de Liberação de Medicamentos/métodos , Ratos , Microscopia Confocal/métodos , Masculino
14.
PLoS One ; 19(4): e0297738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626108

RESUMO

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.


Assuntos
Núcleo Celular , Membrana Nuclear , Membrana Nuclear/metabolismo , Núcleo Celular/metabolismo , Dextranos/metabolismo , Transporte Ativo do Núcleo Celular , Difusão
15.
PLoS One ; 19(4): e0301432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626169

RESUMO

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.


Assuntos
Dextranos , Menisco , Animais , Suínos , Dextranos/metabolismo , Menisco/metabolismo , Meniscos Tibiais/fisiologia , Fibrocartilagem/metabolismo , Fluoresceínas/metabolismo
16.
Molecules ; 29(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38675647

RESUMO

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.


Assuntos
Meios de Contraste , Nanopartículas Magnéticas de Óxido de Ferro , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Nanomedicina Teranóstica , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/química , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Humanos , Ouro/química , Dextranos/química , Gadolínio/química , Propriedades de Superfície , Hipertermia Induzida/métodos , Tamanho da Partícula
17.
Methods Mol Biol ; 2788: 49-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656508

RESUMO

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.


Assuntos
Cromatografia em Gel , Peso Molecular , Polissacarídeos , Cromatografia em Gel/métodos , Polissacarídeos/química , Polissacarídeos/análise , Dextranos/química , Frutanos/química , Frutanos/análise , Calibragem
18.
Int J Biol Macromol ; 267(Pt 2): 131520, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615859

RESUMO

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.


Assuntos
Gelatina , Ácido Hialurônico , Janus Quinase 2 , Doenças Neuroinflamatórias , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Animais , Camundongos , Recuperação de Função Fisiológica/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Gelatina/química , Gelatina/farmacologia , Janus Quinase 2/metabolismo , Dextranos/química , Alicerces Teciduais/química , Microesferas , Fator de Transcrição STAT3/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Modelos Animais de Doenças , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Hidrogéis/química , Hidrogéis/farmacologia
19.
Food Chem ; 449: 139310, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608612

RESUMO

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.


Assuntos
Disponibilidade Biológica , Catequina/análogos & derivados , Emulsificantes , Emulsões , Proteínas do Soro do Leite , Xantofilas , Xantofilas/química , Emulsões/química , Emulsificantes/química , Proteínas do Soro do Leite/química , Animais , Catequina/química , Dextranos/química , Masculino , Ratos , Ratos Sprague-Dawley
20.
Int J Biol Macromol ; 267(Pt 1): 131288, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565365

RESUMO

The unpredictable release behavior of metal nanoparticles/metal ions from metal nanoparticle-loaded hydrogels, without a suitable in situ detection method, is resulting in serious cytotoxicity. To optimize the preparation and design of antibacterial hydrogels for in situ detection of metal nanoparticles, an in-situ detection platform based on the fluorescence signal change caused by the potential surface energy transfer of silver nanoparticles (AgNPs) and carbon dots (CD) through silver mirror reaction and Schiff base reaction was established. The antimicrobial test results show that the composite antimicrobial hydrogel, with lower dosages of AgNPs and CD, exhibited a higher inhibition rate of 99.1 % against E. coli and 99.8 % against S. aureus compared to the single antimicrobial component. This suggests a potential synergistic antimicrobial activity. Furthermore, the fluorescence detection platform was established with a difference of <3 µg between detected values and actual values over a period of 72 h. This demonstrates the excellent in situ detection capability of the hydrogel in antimicrobial-related applications.


Assuntos
Antibacterianos , Dextranos , Escherichia coli , Hidrogéis , Nanopartículas Metálicas , Prata , Staphylococcus aureus , Prata/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Dextranos/química , Testes de Sensibilidade Microbiana , Corantes Fluorescentes/química , Técnicas Biossensoriais/métodos
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