RESUMO
The field of 3-dimensional (3D) bioprinting has significantly expanded capabilities in producing precision-engineered hydrogel constructs, and recent years have seen the development of various stimuli-responsive bio- and photoinks. There is, however, a distinct lack of digital light processing (DLP)-compatible photoinks with thermoresponsivity. To remedy this, this work focuses on formulating and optimizing a versatile ink for DLP printing of thermoresponsive hydrogels, with numerous potential applications in tissue engineering, drug delivery, and adjacent biomedical fields. Photoink optimization was carried out using a multifactorial study design. The optimized photoink yielded crosslinked hydrogels with strong variations in hydrophobicity (contact angles of 44.4°
Assuntos
Resinas Acrílicas , Bioimpressão , Hidrogéis , Bioimpressão/métodos , Hidrogéis/química , Hidrogéis/síntese química , Humanos , Resinas Acrílicas/química , Temperatura , Tinta , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Luz , Impressão Tridimensional , Engenharia Tecidual , AnimaisRESUMO
Zinc metal-organic frameworks have emerged as promising candidates, demonstrating excellent biological properties stemming from the unique characteristics of MOFs and zinc. In this study, we employed a facile method to synthesize a zinc metal-organic framework [Zn(IP)(H2O)] using ultrasound irradiation, with the linker being isophthalic acid (IPA) (1,3-benzene dicarboxylic acid). The parent Zn-MOF and two Ag/Zn-MOF samples prepared via loading and encapsulation methods were comprehensively characterized using various techniques, including FT-IR, XRD, SEM, TEM, N2 adsorption-desorption isotherm, UV-vis spectroscopy and TGA. The parent Zn-MOF and two Ag/Zn-MOF samples exhibited a broad spectrum of antibacterial effects. Remarkably, genomic DNA of P. aeruginosa was effectively degraded by Zn-MOF, further supporting its potent antibacterial results. The free radical inhibition assay demonstrated a 71.0% inhibition under the influence of Zn-MOF. In vitro cytotoxicity activity of Zn-MOF against HepG-2 and Caco-2 cell lines revealed differential cytotoxic effects, with higher cytotoxicity against Caco-2 as explored from the IC50 values. This cytotoxicity was supported by the high binding affinity of Zn-MOF to CT-DNA. Importantly, the non-toxic property of Zn-MOF was confirmed through its lack of cytotoxic effects against normal lung cell (Wi-38). The anti-inflammatory treatment of Zn-MOF achieved 75.0% efficiency relative to the standard Ibuprofen drug. DFT and docking provided insights into the geometric stability of Zn-MOF and its interaction with active amino acids within selected proteins associated with the investigated diseases. Finally, the synthesized Zn-MOF shows promise for applications in cancer treatment, chemoprevention, and particularly antibacterial purposes.
Assuntos
Anti-Inflamatórios , Antineoplásicos , Estruturas Metalorgânicas , Simulação de Acoplamento Molecular , Zinco , Humanos , Zinco/química , Zinco/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Células CACO-2 , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Células Hep G2 , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Teoria da Densidade Funcional , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
While polyphenolic substances stand as excellent antibacterial agents, their antimicrobial properties rely on the auxiliary support of micro-/nanostructures. Despite offering a novel avenue for enhancing polymer performance, controllable fabrication of mesoporous polymeric nanomaterials encounters significant challenges due to intricate intermolecular forces. In this article, mesoporous catechin nanoparticles have been successfully fabricated using a balanced multivariate interaction approach. The harmonization of the water-ethanol ratio and ionic strength effectively balances the forces of hydrogen bonding and π-π stacking, facilitating the controlled assembly of mesostructures. The mesoporous catechin nanoparticles exhibit a uniform spherical structure (â¼100 nm), open mesopores with a diameter of â¼15 nm, and a high surface area of â¼106 m2 g-1. While exhibiting a good biocompatibility and negative surface charge, the mesoporous catechins possess outstanding antibacterial ability and function as an antibiotic mesoformulation without the necessity of loading any drugs. This mesoformulation inhibits 50% in vitro Staphylococcus aureus growth with a low concentration of â¼10 µg mL-1 and achieves complete inhibition at â¼25 µg mL-1. In a mouse wound model, accelerated wound healing and complete closure within 6-8 days are achieved. Proteomics of bacteria reveals that the excellent antibacterial property is attributed to the synergetic effect of mesoformulation's mesostructure and the catechin molecule intervening in bacterial metabolism. Overall, this work may pave a novel way for the future exploration of polymer nanomaterials and antibiotic formulations.
Assuntos
Antibacterianos , Catequina , Nanopartículas , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Catequina/química , Catequina/farmacologia , Nanopartículas/química , Animais , Camundongos , Porosidade , Testes de Sensibilidade Microbiana , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Propriedades de Superfície , Tamanho da Partícula , Cicatrização/efeitos dos fármacosRESUMO
A novel Gd-MOF based on tetrafluoro-terephthalic acid has been synthesized and its structure has been solved using X-ray single crystal diffraction data. The compound, with the formula [Gd2(F4BDC)3·H2O]·DMF, is isostructural with other Ln-MOFs based on the same ligand and has been recently reported. Its crystals were also reduced to nanometer size by employing acetic acid or cetyltrimethylammonium bromide (CTAB) as a modulator. The relaxometric properties of the nanoparticles were evaluated in solution by measuring 1H T1 and T2 as a function of the applied magnetic field and temperature. The biocompatibility of Gd-MOFs was evaluated on murine microglial BV-2 and human glioblastoma U251 cell lines. In both cell lines, Gd-MOFs do not modify the cell cycle profile or the activation levels of ERK1/2 and Akt, which are protein-serine/threonine kinases that participate in many signal transduction pathways. These pathways are fundamental in the regulation of a large variety of processes such as cell migration, cell cycle progression, differentiation, cell survival, metabolism, transcription, tumour progression and others. These data indicate that Gd-MOF nanoparticles exhibit high biocompatibility, making them potentially valuable for diagnostic and biomedical applications.
Assuntos
Gadolínio , Estruturas Metalorgânicas , Gadolínio/química , Gadolínio/farmacologia , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Camundongos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Linhagem Celular Tumoral , Nanoestruturas/química , Halogenação , Sobrevivência Celular/efeitos dos fármacos , Linhagem CelularRESUMO
Both boron neutron capture therapy (BNCT) and photothermal therapy (PTT) have been applied to tumor treatment in clinical. However, their therapeutic efficacy is limited. For BNCT, the agents not only exhibit poor targeting ability but also permit only a single irradiation session within a course due to significant radiation risks. In the context of PTT, despite enhanced selectivity, the limited photothermal effect fails to meet clinical demands. Hence, the imperative arises to combine these two therapies to enhance tumor-killing capabilities and improve the targeting of BNCT agents by leveraging the advantages of PTT agents. In this study, we synthesized a potential responsive agent by linking 4-mercaptophenylboronic acid (MPBA) and IR-780 dye that served as the agents for BNCT and PTT, respectively, which possesses the dual capabilities of photothermal effects and thermal neutron capture. Results from both in vitro and in vivo research demonstrated that IR780-MPBA effectively inhibits tumor growth through its photothermal effect with no significant toxicity. Furthermore, IR780-MPBA exhibited substantial accumulation in tumor tissues and superior tumor-targeting capabilities compared with MPBA, which demonstrated that IR780-MPBA possesses significant potential as a combined antitumor therapy of PTT and BNCT, presenting a promising approach for antitumor treatments.
Assuntos
Antineoplásicos , Terapia por Captura de Nêutron de Boro , Terapia Fototérmica , Animais , Camundongos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Tamanho da Partícula , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Teste de Materiais , Sobrevivência Celular/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , FemininoRESUMO
Hydrated dispersions containing equimolar mixtures of cationic and anionic amphiphiles, referred to as catanionic systems, exhibit synergistic physicochemical properties, and mixing single-chain cationic and anionic lipids can lead to the spontaneous formation of vesicles as well as other phase structures. In the present work, we have characterized two catanionic systems prepared by mixing N-acyltaurines (NATs) and sarcosine alkyl esters (SAEs) bearing 11 and 12 C atoms in the acyl/alkyl chains. Turbidimetric and isothermal titration calorimetric studies revealed that both NATs form equimolar complexes with SAEs having matching acyl/alkyl chains. The three-dimensional structure of the sarcosine lauryl ester (lauryl sarcosinate, LS)-N-lauroyltaurine (NLT) equimolar complex has been determined by single-crystal X-ray diffraction. The LS-NLT equimolar complex is stabilized by electrostatic attraction and multiple hydrogen bonds, including classical, strong N-H···O hydrogen bonds as well as several C-H···O hydrogen bonds between the two amphiphiles. DSC studies showed that both equimolar complexes show single sharp phase transitions. Transmission electron microscopy and dynamic light scattering studies have demonstrated that the LS-NLT catanionic complex assemblies yield stable medium-sized vesicles (diameter 280-350 nm). These liposomes were disrupted at high pH, suggesting that the designed catanionic complexes can be used to develop base-labile drug delivery systems. In vitro studies with these catanionic liposomes showed efficient entrapment (73% loading) and release of the anticancer drug 5-fluorouracil in the physiologically relevant pH range of 6.0-8.0. The release rate was highest at pH 8.0, reaching about 78%, 90%, and 100% drug release at 2, 6, and 12 h, respectively. These observations indicate that LS-NLT catanionic vesicles will be useful for designing drug delivery systems, particularly for targeting organs such as the colon, which are inherently at basic pH.
Assuntos
Materiais Biocompatíveis , Fluoruracila , Tamanho da Partícula , Fluoruracila/química , Estrutura Molecular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Teste de Materiais , Cátions/química , Sarcosina/química , Sarcosina/análogos & derivados , Ésteres/química , Humanos , Lipossomos/químicaRESUMO
The synthesis of bioinspired metal-organic frameworks (MOFs) performed in mild conditions with a high quality is greatly demanded. Moreover, the influence of the morphology and structure of bio-MOFs on the cell interaction and toxicity is important to determine. In this work, we developed an ultrasound (US)-assisted synthesis of HKUST-1 MOFs under mild conditions and investigated the influence of the parameters of synthesis on the morphology, structure, and biological properties of the developed MOFs. It was found that the US power, reaction time, temperature, and type of solvent composition would affect the morphology, size, and yield of the obtained crystals. Employing the optimal synthetic conditions, five types of HKUST-1 MOFs were prepared, achieving highest yields (67.8-96.2%) and different morphologies (octahedral, dodecahedral, icosahedral). The relationship between the morphological features and biological properties of developed bio-MOFs was evaluated and discussed. The cellular association and cytotoxicity of MOF@US and MOF@US-PARG were studied on various cell cultures, i.e. normal mouse embryonic fibroblasts (MEF NF2), chronic myeloid leukemia (K562), and mouse melanoma (B16-F10). The experimental results showed that MOF@US-PARG has a higher percentage of association compared to MOF@US. It has also been shown that the cytotoxicity depends on the concentration and surface modification of the developed MOFs.
Assuntos
Materiais Biocompatíveis , Teste de Materiais , Estruturas Metalorgânicas , Tamanho da Partícula , Camundongos , Animais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Humanos , Sobrevivência Celular/efeitos dos fármacos , Ondas Ultrassônicas , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Propriedades de Superfície , Proliferação de Células/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
While it is well understood that peptides can greatly improve cell-material interactions, it is often challenging to determine the concentration of the peptide which decorates a material. Herein, we describe a straightforward method using readily, synthetically accessible Fmoc peptides and commercially available reagents to measure the concentration of peptides on nanoparticles, surfaces, and hydrogels. To achieve this, the Fmoc protecting group from immobilized peptides is removed under optimized basic conditions. The dibenzofulvene released can be quantified by HPLC or UV-vis spectroscopy, enabling a direct experimental measurement of the concentration of the peptide. We show that we can measure the concentration of a BMP-2 peptide mimic on a hydrogel to determine the concentration required to stimulate osteogenesis of human mesenchymal stem cells. We envision that this methodology will enable a more thorough understanding of the concentration of synthetic peptides decorated on many biomaterials (e.g., nanoparticles, surfaces, hydrogels) to improve deconvolution of the interactions at the cell-material interface.
Assuntos
Materiais Biocompatíveis , Proteína Morfogenética Óssea 2 , Hidrogéis , Células-Tronco Mesenquimais , Peptídeos , Humanos , Peptídeos/química , Peptídeos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Proteína Morfogenética Óssea 2/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Nanopartículas/química , Osteogênese/efeitos dos fármacosRESUMO
Narrow band red-emitting phosphors based on organo-Eu(III) complexes prove their energetic features with surprising performance in smart red/white LEDs, sensing, and biological fields. In this report, a series of unique Eu(III) complexes have been synthesized with coumarin integrated with a class of phenanthroline(Phen)/thiabendazole(TBZ) based ancillary ligands and dibenzoyl methane (DBM)/2-theonyl trifluoroacetone (TTA) as an anionic ligand. The computational study reveals that the TBZ/Phen-based neutral ligands are superior energy harvesters to those other reported analogue neutral ligands. All the Eu-complexes demonstrated outstanding red emission due to electric dipole (ED) transition (5D0 â 7F2) in solid, solution, and thin film with high quantum yield (QY). Theoretical analysis (TD-DFT) and experimental findings describe that the energy transfer (ET) from the ligand's triplet level to the Eu(III) ion is completely occurring. The Eu(III) complexes can potentially be used to fabricate intense hybrid white and red LEDs. All of the fabricated red LEDs revealed high luminous efficiency of radiation (LER) values. The fabricated blue LED based hybrid white LEDs displayed remarkable performance with a low correlated color temperature (5634 K), high color rendering index 88%, and CIE values (x = 0.33; y = 0.342) for 3Eu. By interaction with acid-base vapors, Eu-complexes displayed effectively alterable on-off-on luminescence. Further, cellular imaging shows that Eu-complexes can be a potential biomarker for cancer cell lines.
Assuntos
Cumarínicos , Európio , Teste de Materiais , Fenantrolinas , Európio/química , Cumarínicos/química , Humanos , Fenantrolinas/química , Estrutura Molecular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Tamanho da Partícula , Imagem Óptica , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Medições Luminescentes , Substâncias Luminescentes/química , Substâncias Luminescentes/síntese químicaRESUMO
Chitosan chemical functionalization is a powerful tool to provide novel materials for additive manufacturing strategies. The main aim of this study was the employment of computer-aided wet spinning (CAWS) for the first time to design and fabricate carboxymethyl chitosan (CMCS) scaffolds. For this purpose, the synthesis of a chitosan derivative with a high degree of O-substitution (1.07) and water soluble in a large pH range allowed the fabrication of scaffolds with a 3D interconnected porous structure. In particular, the developed scaffolds were composed of CMCS fibers with a small diameter (< 60 µm) and a hollow structure due to a fast non solvent-induced coagulation. Zn2+ ionotropic crosslinking endowed the CMCS scaffolds with stability in aqueous solutions, pH-sensitive water uptake capability, and antimicrobial activity against Escherichia coli and Staphylococcus aureus. In addition, post-printing functionalization through collagen grafting resulted in a decreased stiffness (1.6 ± 0.3 kPa) and a higher elongation at break (101 ± 9 %) of CMCS scaffolds, as well as in their improved ability to support in vitro fibroblast viability and wound healing process. The obtained results encourage therefore further investigation of the developed scaffolds as antimicrobial wound dressing hydrogels for skin regeneration.
Assuntos
Antibacterianos , Bandagens , Quitosana , Escherichia coli , Staphylococcus aureus , Alicerces Teciduais , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Alicerces Teciduais/química , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Camundongos , Fibroblastos/efeitos dos fármacos , Porosidade , Sobrevivência Celular/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Reagentes de Ligações Cruzadas/química , HumanosRESUMO
Polyphosphoesters (PPEs) represent an innovative class of biodegradable polymers, with the phosphate ester serving as the core repeating unit of their polymeric backbone. Recently, biomaterials derived from functionalized PPEs have garnered significant interest in biomedical applications because of their commendable biocompatibility, biodegradability, and the capacity for functional modification. This review commences with a brief overview of synthesis methodologies and the distinctive properties of PPEs, including thermoresponsiveness, degradability, stealth effect, and biocompatibility. Subsequently, the review delves into the latest applications of PPEs-based nanocarriers for drug or gene delivery and PPEs-based polymeric prodrugs and scaffolds in the biomedical field, presenting several illustrative examples for each application. By encapsulating the advancements of recent years, this review aims to offer an enhanced understanding and serve as a reference for the synthesis and biomedical applications of functional PPEs.
Assuntos
Materiais Biocompatíveis , Polímeros , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Humanos , Polímeros/química , Polímeros/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Animais , Ésteres/químicaRESUMO
3D bioprinting, a significant advancement in biofabrication, is renowned for its precision in creating tissue constructs. Collagen, despite being a gold standard biomaterial, faces challenges in bioink formulations due to its unique physicochemical properties. This study introduces a novel, neutral-soluble, photocrosslinkable collagen maleate (ColME) that is ideal for 3D bioprinting. ColME was synthesized by chemically modifying bovine type I collagen with maleic anhydride, achieving a high substitution ratio that shifted the isoelectric point to enhance solubility in physiological pH environments. This modification was confirmed to preserve the collagen's triple-helix structure substantially. Bioprinting parameters for ColME were optimized, focusing on adjustments to the bioink concentration, extrusion pressure, nozzle speed, and temperature. Results demonstrated that lower temperatures and smaller nozzle sizes substantially improved the print quality of grid structures. Additionally, the application of intermittent photo-crosslinking facilitated the development of structurally robust 3D multilayered constructs, enabling the stable fabrication of complex tissues. Cell viability assays showed that encapsulated cells within the ColME matrix maintained high viability after printing. When compared to methacrylated gelatin, ColME exhibited superior mechanical strength, resistance to enzymatic digestion, and overall printability, positioning it as an outstanding bioink for the creation of durable, bioactive 3D tissues.
Assuntos
Bioimpressão , Maleatos , Impressão Tridimensional , Animais , Maleatos/química , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Reagentes de Ligações Cruzadas/química , Processos Fotoquímicos , Engenharia Tecidual , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Tinta , Alicerces Teciduais/química , Humanos , Colágeno Tipo I/químicaRESUMO
Impaired wound healing in diabetic wounds is common due to infection, inflammation, less collagen synthesis, and vascularization. Diabetic wound healing in patients is still a challenge and needs an ideal wound dressing to treat and manage diabetic wounds. Herein, an efficacious wound dressing biomaterial was fabricated by cross-linking oxidized isabgol (Oisab) and chitosan (Cs) via trisodium trimetaphosphate and Schiff base bonds. l-Arginine (l-Arg) was incorporated as a bioactive substance in the Oisab + Cs scaffold to promote cell adhesion, cell proliferation, collagen synthesis, and vascularization. The fabricated scaffolds showed microporous networks in the scanning electron microscopy analysis. The scaffold also possessed excellent hemocompatibility. In vitro studies using fibroblasts (L929 and human dermal fibroblast cells) confirmed the cytocompatibility of these scaffolds. The results of the in vivo chicken chorioallantoic membrane assay confirmed the proangiogenic activity of the Oisab + Cs + l-Arg scaffolds. The wound-healing potential of these scaffolds was studied in streptozotocin-induced diabetic rats. This in vivo study showed that the period of epithelialization in the Oisab + Cs + l-Arg scaffold-treated wounds was 21.67 ± 1.6 days, which was significantly faster than the control (30.33 ± 2.5 days). Histological and immunohistochemical studies showed that the Oisab + Cs + l-Arg scaffolds significantly accelerated the rate of wound contraction by reducing inflammation, improving collagen synthesis, and promoting neovascularization. These findings suggest that the Oisab + Cs + l-Arg scaffolds could be beneficial in treating diabetic wounds in clinical applications.
Assuntos
Arginina , Quitosana , Colágeno , Diabetes Mellitus Experimental , Teste de Materiais , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Colágeno/química , Arginina/química , Arginina/farmacologia , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Humanos , Masculino , Tamanho da Partícula , Neovascularização Fisiológica/efeitos dos fármacos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/síntese química , Camundongos , Ratos Sprague-Dawley , OxirreduçãoRESUMO
Leishmaniasis, attributed to the protozoan parasite Leishmania, manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedyâa citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against L. donovani Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.
Assuntos
Anfotericina B , Antiprotozoários , Ouro , Nanopartículas Metálicas , Ouro/química , Ouro/farmacologia , Anfotericina B/farmacologia , Anfotericina B/química , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/síntese química , Nanopartículas Metálicas/química , Tamanho da Partícula , Nanoconjugados/química , Teste de Materiais , Leishmania donovani/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , HumanosRESUMO
Polymethyl methacrylate (PMMA) based biomaterials have been widely utilized in clinics. However, currently, PMMA catalyzed by benzoyl peroxide (BPO) exhibits disquieting disadvantages including an exothermic polymerization reaction and a lack of bioactivity. Here, we first designed three industrial-scale synthesis methods for high-purity butoxydibutylborane (BODBB), achieving purity levels greater than 95% (maximum: 97.6%) and ensuring excellent fire safety. By utilizing BODBB as a catalyst, the highest polymerization temperature of PMMA bone cement (PMMA-BODBB) reached only 36.05 °C, ensuring that no thermal damage occurred after implantation. Compared to PMMA catalyzed by BPO and partially oxidized tributylborane (TBBO, catalyst of Super Bond C&B), PMMA-BODBB exhibited superior cell adhesion, proliferation, and osteogenesis, attributed to the reduced release of free radicals and toxic monomer, and moderate bioactive boron release. After injection into a 5 mm defect in the rat cranial bone, PMMA-BODBB demonstrated the highest level of osteointegration. This work not only presents an industrial-scale synthesis of high-purity BODBB, but also offers an innovative PMMA biomaterial system with intrinsic biocompatibility and osseointegration, paving the way for the next generation of PMMA-based biomaterials with broader applications.
Assuntos
Materiais Biocompatíveis , Cimentos Ósseos , Osseointegração , Polimerização , Polimetil Metacrilato , Polimetil Metacrilato/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Catálise , Ratos , Cimentos Ósseos/química , Cimentos Ósseos/síntese química , Osseointegração/efeitos dos fármacos , Boranos/química , Boranos/síntese química , Proliferação de Células/efeitos dos fármacos , Teste de Materiais , Ratos Sprague-Dawley , Camundongos , Adesão Celular/efeitos dos fármacosRESUMO
In this study, we employed a combination of electrospinning and electrospray techniques to fabricate wound dressings with a particle-fiber structure, providing dual characteristics of oxygen-releasing and intrinsic antioxidant properties, simultaneously. The electrospun part of the dressing was prepared from a blend of polycaprolactone/gallic acid-grafted-gelatin (GA-g-GE), enabling intrinsic ROS scavenging. To the best of our knowledge, this is the first time that PCL/GA-g-GE was fabricated by electrospinning. Furthermore, polyvinyl pyrrolidone (PVP) microparticles, containing calcium peroxide nanoparticles (CNPs), were considered as the oxygen production agent through the electrospray part. The CNP content was 1% and 3% w/w of PVP while biopolymer:PCL was 10% w/w. The fabricated structures were characterized in terms of fiber/particle morphology, elemental analysis, oxygen release behavior, ROS inhibition capacity, and water contact angle assessments. The covalent bonding of gallic acid to gelatin was confirmed by 1H-NMR, UV spectroscopy, and FTIR. According to the SEM results, the morphology of the prepared PCL/biopolymer fibers was bead-free and with a uniform average diameter. The analysis of released oxygen showed that by increasing the weight percentage of CNPs from 1 to 3 wt%, the amount of released oxygen increased from 120 mmHg to 195 mmHg in 24 h, which remained almost constant until 72 h. The obtained DPPH assay results revealed that the introduction of GA-g-GE into the fibrous structure could significantly improve the antioxidant properties of wound dressing compared to the control group without CNPs and modified gelatine. In vitro, the fabricated wound dressings were evaluated in terms of biocompatibility and the potential of the dressing to protect human dermal fibroblasts under oxidative stress and hypoxia conditions by an MTT assay. The presence of GA-g-GE led to remarkable protection of the cells against oxidative stress and hypoxia conditions. In vivo studies revealed that the incorporation of intrinsic ROS inhibition and oxygen-releasing properties could significantly accelerate the wound closure rate during the experimental period (7, 14, and 21 days). Additionally, histopathological investigations in terms of H&E and Masson's trichrome staining showed that the incorporation of the two mentioned capabilities remarkably facilitated the wound-healing process.
Assuntos
Antioxidantes , Bandagens , Oxigênio , Poliésteres , Antioxidantes/química , Antioxidantes/farmacologia , Oxigênio/química , Animais , Poliésteres/química , Ácido Gálico/química , Ácido Gálico/farmacologia , Gelatina/química , Tamanho da Partícula , Cicatrização/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Nanopartículas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese químicaRESUMO
Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton's reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.
Assuntos
Materiais Biocompatíveis , Hidrogéis , Peróxido de Hidrogênio , Teste de Materiais , Hidrogéis/química , Hidrogéis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologia , Peróxido de Hidrogênio/química , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/síntese química , Polímeros/química , Tamanho da Partícula , Ferro/química , Estrutura Molecular , Humanos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Wound healing represents a complex biological process crucial for tissue repair and regeneration. In recent years, biomaterial-based scaffolds loaded with bioactive compounds have emerged as promising therapeutic strategies to accelerate wound healing. In this study, we investigated the properties and wound healing effects of cryogels loaded with calcium peroxide (CP) and berberine (BB). The cryogels were synthesized through a cryogenic freezing technique and displayed pore diameters of 83 ± 39 µm, with porosity exceeding 90%. Following 20 days of degradation, the percentage of remaining weight for GPC and GPC-CP-BB cryogels was determined to be 12.42 ± 2.45% and 10.78 ± 2.08%, respectively. Moreover, the swelling ratios after 3 minutes for GPC and GPC-CP-BB were found to be 22.10 ± 0.05 and 21.00 ± 0.07, respectively. In vitro investigations demonstrated the cytocompatibility of the cryogels, with sufficient adhesion and proliferation of fibroblast (NIH-3T3) cells observed on the scaffolds, along with their hemocompatibility. Furthermore, the cryogels exhibited sustained release kinetics of both calcium peroxide and berberine, ensuring prolonged therapeutic effects at the wound site. In vivo assessment using a rat model of full-thickness skin wounds demonstrated accelerated wound closure rates in animals treated with the GPC-CP-BB scaffold compared to controls. Histological analysis revealed enhanced granulation tissue formation, re-epithelialization, and collagen deposition in the GPC-CP-BB group. Overall, our findings suggest that the scaffold loaded with CP and BB holds great promise as a therapeutic approach for promoting wound healing. Its multifaceted properties offer a multifunctional platform for localized delivery of therapeutic agents while providing mechanical support and maintaining a favorable microenvironment for tissue regeneration.
Assuntos
Berberina , Criogéis , Peróxidos , Cicatrização , Berberina/química , Berberina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Criogéis/química , Camundongos , Ratos , Células NIH 3T3 , Peróxidos/química , Peróxidos/farmacologia , Proliferação de Células/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Ratos Sprague-Dawley , Masculino , PorosidadeRESUMO
Weak binding of carbohydrates with protein receptors possesses serious drawbacks in the advancement of therapeutics; however, the development of strategies for multipoint interactions between carbohydrates and protein can overcome these challenges. One such method is developed in this work where glycopolymer-grafted silica nanoparticles with a large number of carbohydrate units are prepared for the interactions with multiple binding sites of the protein. First, a glycomonomer, ß-d-galactose-hydroxyethyl methacrylate (ß-GEMA), was synthesized in a two-step process by coupling ß-d-galactose pentaacetate and hydroxyethyl methacrylate (HEMA), followed by deacetylation for the preparation of poly(ß-GEMA) glycopolymers (GPs). Further, the poly(ß-GEMA) chains were grafted onto the silica nanoparticle (SiNP) surface by utilizing the "grafting-from" strategy of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare p(ß-GEMA)-grafted SiNPs (GNPs). Five different chain lengths ranging from 10 to 40 kDa of the GPs and the GNPs were prepared, and various characterization techniques confirmed the formation of GPs and grafting of the GPs on the SiNP surface. The particle size of GNPs and the number of GPs grafted on the SiNP surface showed a strong dependence on the chain length of the GPs. Further, the GNPs were subjected to a binding study with ß-galactose-specific protein peanut agglutinin (PNA). A much stronger binding in the case of GNPs was observed with an association constant â¼320 times and â¼53 times than that of the monomeric methyl-ß-d-galactopyranoside and the GPs, respectively. Additionally, the binding of the PNA with GNPs and GPs was also studied with varying chain lengths to understand the effects of the chain length on the binding affinity. A clear increase in binding constants was observed in the case of GNPs with increasing chain length of grafted GPs, attributed to the enhanced enthalpic and entropic contributions. This work holds its uniqueness in these improved interactions between carbohydrates and proteins, which can be used for carbohydrate-based targeted therapeutics.
Assuntos
Galactose , Nanopartículas , Dióxido de Silício , Nanopartículas/química , Galactose/química , Dióxido de Silício/química , Tamanho da Partícula , Teste de Materiais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Lectinas/química , Lectinas/metabolismo , Polímeros/química , Polímeros/síntese química , Ligação Proteica , Propriedades de SuperfícieRESUMO
Floxuridine is a potential clinical anticancer drug for the treatment of various cancers. However, floxuridine typically causes unfavorable side effects due to its very poor tumor selectivity, and, hence, there is a high demand for the development of novel approaches that permit the targeted delivery of floxuridine into cancerous cells. Herein, the design and synthesis of an esterase-responsive multifunctional nanoformulation for the targeted delivery of floxuridine in esterase-overexpressed cancer cells is reported. Photopolymerization of floxuridine-tethered lipoic acid results in the formation of amphiphilic floxuridine-tethered poly(disulfide). Self-assembly of the amphiphilic polymer results in the formation of nanoparticles with floxuridine decorated on the surfaces of the particles. Integration of aptamer DNA for nucleolin onto the surface of the nanoparticle is demonstrated by exploring the base-pairing interaction of floxuridine with adenine. Targeted internalization of the aptamer-decorated nanoparticle into nucleolin-expressed cancer cells is demonstrated. Esterase triggered cleavage of the ester bond connecting floxuridine with the polymer backbone, and the subsequent targeted delivery of floxuridine into cancer cells is also shown. Excellent therapeutic efficacy is observed both in vitro and also in the 3D tumor spheroid model. This noncovalent strategy provides a simple yet effective strategy for the targeted delivery of floxuridine into cancer cells in a less laborious fashion.