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Skin interstitial fluid (ISF) has emerged as a significant reservoir of biomarkers for disease diagnosis and prevention. Microneedle (MN) patches are regarded as an optimal platform for ISF extraction from the skin due to their non-invasive nature. However, challenges such as prolonged sampling durations and complex detection procedures impede timely metabolic analysis. In this investigation, we amalgamated MN technology with immobilized enzyme technology to fabricate a dual-layer MN patch integrating sampling and detection functionalities, thereby enabling in-situ colorimetric detection of hyperglycemia. The tip layer of the patch, comprising polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) MN, was synthesized utilizing a chemical crosslinking approach for the first time, with glucose oxidase (GOx) being incorporated. The hydrophilicity of CMCS expedited the extraction process, facilitating the retrieval of approximately 10 mg of ISF within 10 min. The backing layer consisted of an immobilized polyvinyl alcohol-chitosan-horseradish peroxidase (PVA-CS-HRP) hydrogel film loaded with 3,3', 5,5'-tetramethylbenzidine (TMB). Incorporating macromolecular polymer PVA and CS for HRP immobilization addressed the issue of poor stability associated with traditional natural enzymes, thereby enhancing the sensitivity of the reaction system. The in-situ colorimetric sensor facilitated minimally invasive ISF extraction and swift conversion of glucose levels into detectable color changes.
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The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment.
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Combination therapy is an important direction of continuous exploration in the field of medicine, with the core goals of improving treatment efficacy, reducing adverse reactions, and optimizing clinical outcomes. Machine learning technology holds great promise in improving the prediction of drug synergy combinations. However, most studies focus on single disease-oriented collaborative predictive models or involve excessive feature categories, making it challenging to predict the majority of new drugs. To address these challenges, the DrugSK comprehensive model was developed, which utilizes SMILES-BERT to extract structural information from 3492 drugs and trains on reactions from 48,756 drug combinations. DrugSK is an integrated learning model capable of predicting interactions among various drug categories. First, the primary learner is trained from the initial data set. Random forest, support vector machine, and XGboost model are selected as primary learners and logistic regression as secondary learners. A new data set is then "generated" to train level 2 learners, which can be thought of as a prediction for each model. Finally, the results are filtered using logistic regression. Furthermore, the combination of the new antibacterial drug Drafloxacin with other antibacterial agents was tested. The synergistic effect of Drafloxacin and Isavuconazonium in the fight against Candida albicans has been confirmed, providing enlightenment for the clinical treatment of skin infection. DrugSK's prediction is accurate in practical application and can also predict the probability of the outcome. In addition, the tendency of Drafloxacin and antifungal drugs to be synergistic was found. The development of DrugSK will provide a new blueprint for predicting drug combination synergies.
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Aprendizado de Máquina , Humanos , Combinação de Medicamentos , Antibacterianos/farmacologia , Antibacterianos/química , Candida albicans/efeitos dos fármacos , Quimioterapia CombinadaRESUMO
Introduction: In recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there is less research on bibliometrics. The purpose of this study is to conduct a comprehensive bibliometric analysis of graph neural network applications in drug discovery in order to identify current research hotspots and trends, as well as serve as a reference for future research. Methods: Publications from 2017 to 2023 about the application of graph neural network in drug discovery were collected from the Web of Science Core Collection. Bibliometrix, VOSviewer, and Citespace were mainly used for bibliometric studies. Results and Discussion: In this paper, a total of 652 papers from 48 countries/regions were included. Research interest in this field is continuously increasing. China and the United States have a significant advantage in terms of funding, the number of publications, and collaborations with other institutions and countries. Although some cooperation networks have been formed in this field, extensive worldwide cooperation still needs to be strengthened. The results of the keyword analysis clarified that graph neural network has primarily been applied to drug-target interaction, drug repurposing, and drug-drug interaction, while graph convolutional neural network and its related optimization methods are currently the core algorithms in this field. Data availability and ethical supervision, balancing computing resources, and developing novel graph neural network models with better interpretability are the key technical issues currently faced. This paper analyzes the current state, hot spots, and trends of graph neural network applications in drug discovery through bibliometric approaches, as well as the current issues and challenges in this field. These findings provide researchers with valuable insights on the current status and future directions of this field.
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Constructing metal-organic gels (MOGs) with enzyme-catalyzed activity and studying their catalytic mechanism are crucial for the development of novel nanozyme materials. In this study, a Co@Fe MOG with excellent peroxidase activity was developed by a simple and mild one-pot process. The results showed that the material exhibited almost a single peroxidase activity under optimal pH conditions, which allowed it to attract and oxidize the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Based on the active electron transfer between the metal centers and the organic ligand in the synthetic material, the Co@Fe MOG-H2O2-TMB system was verified to be able to detect H2O2 and citric acid (CA). The catalytic microenvironment formed by the adsorption and the catalytic center accelerated the electron-transfer rate, which expedited the generation of hydroxyl radicals (ËOH, a kind of reactive oxygen species (ROS)) in the presence of H2O2. The persistence and high intensity of ËOH generation were proven, which would endow Co@Fe MOG with a certain antibacterial ability, promoting the healing of bacteria-infected wounds. In conclusion, this study contributes to the development efforts toward the application systems of nanozymes for marker detection and antibacterial activity.
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Antibacterianos , Cobalto , Colorimetria , Géis , Ferro , Peroxidase , Antibacterianos/farmacologia , Antibacterianos/química , Ferro/química , Cobalto/química , Colorimetria/métodos , Géis/química , Peroxidase/metabolismo , Peroxidase/química , Porosidade , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/química , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , CatáliseRESUMO
Cascade reactions are described as efficient and versatile tools, and organized catalytic cascades can significantly improve the efficiency of chemical interworking between nanozymes. They have attracted great interest in many fields such as chromogenic detection, biosensing, tumor diagnosis, and therapy. However, how to selectively kill tumor cells by enzymatic reactions without harming normal cells, as well as exploring two or more enzyme-engineered nanoreactors for cascading catalytic reactions, remain great challenges in the field of targeted and specific cancer diagnostics and therapy. The latest research advances in nanozyme-catalyzed cascade processes for cancer diagnosis and therapy are described in this article. Here, various sensing strategies are summarized, for tumor-specific diagnostics. Targeting mechanisms for tumor treatment using cascade nanozymes are classified and analyzed, "elements" and "dimensions" of cascade nanozymes, types, designs of structure, and assembly modes of highly active and specific cascade nanozymes, as well as a variety of new strategies of tumor targeting based on the cascade reaction of nanozymes. Finally, the integrated application of the cascade nanozymes systems in tumor-targeted and specific diagnostic therapy is summarized, which will lay the foundation for the design of more rational, efficient, and specific tumor diagnostic and therapeutic modalities in the future.
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With the rapid development of society, food safety to public health has been a topic that cannot be ignored. In recent years, lanthanide-based materials are studied to be potential candidates in the detection of food samples. Cerium (Ce)-based materials (such as Ce ions, CeO2, Ce-metal organic framework (Ce-MOF), etc.) have also attracted more attention in food detection by virtue of colorimetric, fluorescence, sensing, and other methods. This is because the mixed valence of Ce (Ce3+ and Ce4+), the formation of oxygen vacancies, and their optical and electrochemical properties. In this review, Ce-based materials will be introduced and discussed in the field of food detection, including biogenesis, construction, catalytic mechanisms, combination, and applications. In addition, the current challenges and future development trend of these Ce-based materials in food safety detection are also proposed and discussed. Therefore, it is meaningful to explore the Ce-based materials for detection of biomarkers in food samples.
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Cério , Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Cério/química , Estruturas Metalorgânicas/química , Oxigênio/química , ColorimetriaRESUMO
Nanoparticles (NPs) have been designed for the treatment of tumors increasingly. However, the drawbacks of single-size NPs are still worth noting, as their circulation and metabolism in the blood are negatively correlated with their accumulation at the tumor site. If the size of single-size NPs is too small, it will be quickly cleared in the blood circulation, while, the size is too large, the distribution of NPs in the tumor site will be reduced, and the widespread distribution of NPs throughout the body will cause systemic toxicity. Therefore, a class of variable-size NPs with metal organic frameworks (MOFs) as the main carrier, and size conversion in compliance with the characteristics of the tumor microenvironment (TME), was designed. MOF-based variable-size NPs can simultaneously extend the time of blood circulation and metabolism, then enhance the targeting ability of the tumor site. In this review, MOF NPs are categorized and exemplified from a new perspective of NP size variation; the advantages, mechanisms, and significance of MOF-based variable-size NPs were summarized, and the potential and challenges in delivering anti-tumor drugs and multimodal combination therapy were discussed.
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Antineoplásicos , Estruturas Metalorgânicas , Nanopartículas , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Estruturas Metalorgânicas/química , Humanos , Nanopartículas/química , Nanopartículas/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
Diabetic wounds in a state of high glucose are refractory to treatment and healing, especially if they are infected with bacteria. Herein, a novel nanocomposite (CIP/GOx@ZIF-8) was synthesized by loading ciprofloxacin hydrochloride (CIP) and glucose oxidase (GOx) into zeolitic imidazole framework-8 (ZIF-8) that exhibited good glucose sensitivity and catalytic activity. The high glucose in diabetic wounds could be decomposed into hydrogen peroxide (H2O2) and gluconic acid via the catalysis of GOx, which further destroyed CIP/GOx@ZIF-8 to release Zn2+ and cargos. The combination of glucose starvation, Zn2+, H2O2 and CIP could elevate the antibacterial effect and reduce bacterial resistance. Subsequently, the nanocomposite was fabricated into dissolving microneedles (CIP/GOx@ZIF-8 MNs) using polyvinylpyrrolidone (PVP). The microneedles exhibited good mechanical strength, puncture performance, dissolving performance, glucose responsiveness, antibacterial performance and biocompatibility. For in vivo wound healing, CIP/GOx@ZIF-8 MNs with good biosafety facilitated neovascularization and collagen deposition as well as reduced inflammation, and the wounds were almost healed after treatment. This multimodal therapeutic strategy is created to provide a unique treatment for infected diabetic wounds.
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Diabetes Mellitus , Nanocompostos , Zeolitas , Humanos , Glucose , Peróxido de Hidrogênio , Glucose Oxidase , AntibacterianosRESUMO
BACKGROUND: Regular blood glucose monitoring is very important for diabetic patients. The composition of skin interstitial fluid (ISF) is similar to that of blood, which can be used for daily blood sugar detection and disease care. However, most methods of ISF extraction have complicated steps, may cause skin damage, and can only extract a limited amount of ISF, resulting in low detection efficiency. Therefore, it is very necessary to develop a detection method that can not only extract a large amount of ISF safely, efficiently, and conveniently, but also realize rapid detection of glucose level in ISF. RESULTS: Here, we developed a gold nanoparticle (AuNP)-based swellable colorimetric MN patch with minimally invasive sampling function and real-time ISF glucose analysis ability. The MN patch could quickly absorb a large amount of skin ISF, and 60.2 mg of ISF was extracted within 10 min in vitro. It was divided into two layers: the tip layer was embedded with AuNPs with glucose oxidase (GOx)-like activity, which catalyzed the oxidation of glucose extracted from ISF and produced hydrogen peroxide (H2O2); horseradish peroxidase (HRP) encapsulated in the backing layer catalyzed the oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) by H2O2 to produce oxTMB, which led to a visible color shift in the backing layer. The ISF glucose level was judged by naked eyes and further quantified by color analysis with Image J software. As a result, the colorimetric MN patch successfully identified the normal blood sugar and hyperglycemia state in vivo. SIGNIFICANCE: The colorimetric MN patch combined in-situ colorimetric sensing based on AuNP nanozyme with MN patch, which detected glucose level without blood drawing, increasing patients' compliance and reducing detection steps and time. Compared with the detection methods based on natural nanozymes, our method had better stability and sensitivity to complex environments (extreme pH and high temperature, etc.) in actual detection.
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Glicemia , Nanopartículas Metálicas , Humanos , Glicemia/análise , Ouro/química , Glucose Oxidase/química , Automonitorização da Glicemia , Colorimetria/métodos , Peróxido de Hidrogênio/química , Nanopartículas Metálicas/química , Glucose/análiseRESUMO
Skin interstitial fluid (ISF) has been an alternative source in the field of biomarkers analysis. This work developed swellable hydrogel microneedles (MNs) composed of polyvinyl alcohol and sodium alginate by chemical crosslinking (PVA/SA). Here, PVA/SA was firstly used to fabricate hydrogel MNs, achieving a swellable ratio of 150 % and a rapid extraction of 6.4 mg ISF in 15 min. To replace expensive and non-reusable test kits, hydrogel MNs based on composite nanozyme with high oxidase-like activity were successfully developed to recover and detect biomarkers. The nanozyme was composed of MnO2-modified mixed valence cerium-metal organic frame (MCM). MCM was characterized by multiple techniques to further confirm its composition and structure. MCM combined with the reduction reaction of glutathione (GSH) with oxidized substrate to achieve a colorimetric GSH detection, which had a detection limit (LOD, 0.36 µM) of GSH. The hydrogel MNs based on MCM (MCM-MNs) were firstly applied to the rapid detection of GSH in ISF. All in all, this method combines the advantages of nanozyme and hydrogel MNs to achieve a timely and minimally invasive analysis, which provides a new dimension for the in vivo detection of GSH by skin ISF and holds great implications in biomedical and bioanalysis fields.
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Cério , Cério/química , Hidrogéis , Compostos de Manganês , Óxidos , BiomarcadoresRESUMO
Heavy metal pollution poses a major threat to human health, and developing a user-deliverable heavy metal detection strategy remains a major challenge. In this work, two-mode Hg2+ sensing platforms based on the tunable cobalt metal-organic framework (Co-MOF) active site strategy are constructed, including a colorimetric, and an electrochemical assay using a personal glucose meter (PGM) as the terminal device. Specifically, thymine (T), a single, adaptable nucleotide, is chosen to replace typical T-rich DNA aptamers. The catalytic sites of Co-MOF are tuned competitively by the specific binding of T-Hg2+-T, and different signal output platforms are developed based on the different enzyme-like activities of Co-MOF. DFT calculations are utilized to analyze the interaction mechanism between T and Co-MOF with defect structure. Notably, the two-mode sensing platforms exhibit outstanding detection performance, with LOD values as low as 0.5 nM (colorimetric) and 3.69 nM (PGM), respectively, superior to recently reported nanozyme-based Hg2+ sensors. In real samples of tap water and lake water, this approach demonstrates an effective recovery rate and outstanding selectivity. Surprisingly, the method is potentially versatile and, by exchanging out T-Hg2+-T, can also detect Ag+. This simple, portable, and user-friendly Hg2+ detection approach shows plenty of promise for application in the future.
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Mercúrio , Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/química , Domínio Catalítico , Cobalto/química , Água/química , Mercúrio/química , ColorimetriaRESUMO
Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation, needle-stick injuries, and primary systemic immunity. Inhalable vaccines exhibited unique advantages due to their small dose, easy to use, quick effect, and simultaneous induction of mucosal and systemic responses. Facing global pandemics, especially the coronavirus disease 2019 (COVID-19), a majority of inhalable vaccines are in preclinical or clinical trials. A better understanding of advanced delivery technologies of inhalable vaccines may provide new scientific insights for developing inhalable vaccines. In this review article, detailed immune mechanisms involving mucosal, cellular, and humoral immunity were described. The preparation methods of inhalable vaccines were then introduced. Advanced nanotechnologies of inhalable vaccines containing inhalable nucleic acid vaccines, inhalable adenovirus vector vaccines, novel adjuvant-assisted inhalable vaccines, and biomaterials for inhalable vaccine delivery were emphatically discussed. Meanwhile, the latest clinical progress in inhalable vaccines for COVID-19 and tuberculosis was discussed.
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COVID-19 , Vacinas , Humanos , Imunidade nas Mucosas , Vacinas contra COVID-19 , Nanotecnologia/métodos , COVID-19/prevenção & controleRESUMO
Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.
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Nanopartículas , Trombose , Trombose Venosa , Humanos , Polímeros/uso terapêutico , Fibrinolíticos/uso terapêutico , Pirróis/uso terapêutico , Preparações Farmacêuticas , Biomimética , Qualidade de Vida , Trombose Venosa/tratamento farmacológico , Trombose/tratamento farmacológico , Nanopartículas/uso terapêuticoRESUMO
Supramolecular hydrogels bound by hydrogen bonding, host-guest, hydrophobic, and other non-covalent interactions are among the most attractive biomaterials available. Supramolecular hydrogels have attracted extensive attention due to their inherent dynamic reversibility, self-healing, stimuli-response, excellent biocompatibility, and near-physiological environment. However, the inherent contradiction between non-covalent interactions and mechanical strength makes the practical application of supramolecular hydrogels a great challenge. This review describes the mechanical strength of hydrogels mediated by supramolecular interactions, and focuses on the potential strategies for enhancing the mechanical strength of supramolecular hydrogels and illustrates their applications in related fields, such as flexible electronic sensors, wound dressings, and three-dimensional (3D) scaffolds. Finally, the current problems and future research prospects of supramolecular hydrogels are discussed. This review is expected to provide insights that will motivate more advanced research on supramolecular hydrogels.
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Materiais Biocompatíveis , Hidrogéis , Hidrogéis/química , Materiais Biocompatíveis/química , Interações Hidrofóbicas e HidrofílicasRESUMO
Various binding modes of tunable metal organic frameworks (MOFs) and functional DNAzymes (Dzs) synergistically catalyze the emergence of abundant functional nanoplatforms. Given their serial variability in formation, structural designability, and functional controllability, Dzs@MOFs tend to be excellent building blocks for the precise "intelligent" manufacture of functional materials. To present a clear outline of this new field, this review systematically summarizes the progress of Dz integration into MOFs (MOFs@Dzs) through different methods, including various surface infiltration, pore encapsulation, covalent binding, and biomimetic mineralization methods. Atomic-level and time-resolved catalytic mechanisms for biosensing and imaging are made possible by the complex interplay of the distinct molecular structure of Dzs@MOF, conformational flexibility, and dynamic regulation of metal ions. Exploiting the precision of DNAzymes, MOFs@Dzs constructed a combined nanotherapy platform to guide intracellular drug synthesis, photodynamic therapy, catalytic therapy, and immunotherapy to enhance gene therapy in different ways, solving the problems of intracellular delivery inefficiency and insufficient supply of cofactors. MOFs@Dzs nanostructures have become excellent candidates for biosensing, bioimaging, amplification delivery, and targeted cancer gene therapy while emphasizing major advancements and seminal endeavors in the fields of biosensing (nucleic acid, protein, enzyme activity, small molecules, and cancer cells), biological imaging, and targeted cancer gene delivery and gene therapy. Overall, based on the results demonstrated to date, we discuss the challenges that the emerging MOFs@Dzs might encounter in practical future applications and briefly look forward to their bright prospects in other fields.
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DNA Catalítico , Estruturas Metalorgânicas , Nanoestruturas , Estruturas Metalorgânicas/química , Sistemas de Liberação de Medicamentos/métodos , ProteínasRESUMO
The Keteling capsule (KC) is a traditional Chinese medicine (TCM) made from the dried extract of Ficus microphylla and an appropriate amount of chlorpheniramine maleate. It is widely used to treat cough and relieve asthma. Despite its extensive usage, a rapid and comprehensive quality evaluation strategy for KC remains a challenge. This study introduces an electrochemical fingerprint analysis technique, in addition to the commonly employed HPLC fingerprints, for efficient and convenient quality evaluation. Moreover, a cost-effective, rapid, and accurate multi-component quantification technique known as the "Multi-markers assay by the monolinear method (MAML)" and the "FT-IR quantitative model" were explored. The HPLC fingerprints were evaluated using a systematically quantified fingerprint method, while the electrochemical fingerprints, based on the Belousov-Zhabotinsky oscillation reaction principle, were effectively analyzed and characterized using oxidation induction times and oscillation lifetimes. Multi-component quantitative analysis was carried out through the MAML and FT-IR quantitative models. The HPLC fingerprint successfully classified the 22 samples into eight grades with excellent discrimination. Active ingredient content analysis was achieved using reliable parameters obtained from electrochemical fingerprinting. The no significant difference in the quantitative results proves the accuracy of the MAML method. Additionally, successful FT-IR quantitative prediction models were developed for chlorogenic acid, isovitexin, and chlorpheniramine maleate. This study offers a dependable and effective approach for enhancing the quality control of KC, and it can provide new insights for improving the quality analysis methods in the field of TCM.
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Bioensaio , Clorfeniramina , Cápsulas , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido ClorogênicoRESUMO
Microneedle (MN) systems for painless transdermal drug delivery have been well developed over the past few years to overcome the problems of subcutaneous injections. Hyaluronic acid (HA) is a glycosaminoglycan that exists widely in living organisms, and chitosan (CS) is the only basic polysaccharide among natural polysaccharides, both of which have good biodegradability. Molybdenum sulfide (MoS2) is a typical layered transition metal disulfide with a two-dimensional structure and many unique physicochemical properties. However, its applicability in antimicrobial MNs is unknown. Therefore, in this paper, the antibacterial properties of the nanocomposites formed by MoS2 for MN preparation were investigated by combining the carbohydrate CS with antibacterial properties. The mechanical properties, irritation and blood compatibility of the prepared dissolving HA MN patches were investigated. Finally, the antibacterial properties of the composite MNs against Escherichia coli and Staphylococcus aureus were studied in vitro to evaluate the antibacterial properties of the developed antibacterial nanocomposite-loaded MNs. In addition, the results of the in vivo wound healing experiments showed that the dissolving antimicrobial MNs we prepared had a potential therapeutic effect on wound healing.
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Quitosana , Quitosana/química , Ácido Hialurônico/química , Molibdênio/farmacologia , Molibdênio/química , Antibacterianos/farmacologia , Antibacterianos/química , Administração CutâneaRESUMO
With the increasing prevalence of drug-resistant bacterial infections and frequent occurrences of slow wound healing, the development of novel antibacterial wound dressings has become a serious challenge. Hydrogel dressings have attracted extensive attention on wound healing due to their unique three-dimensional network structures and properties. However, it is a challenge to develop natural long-acting antibacterial hydrogels with multiple functions such as excellent cell affinity, wet adhesion and mechanical properties. Inspired by the wound healing mechanism and adhesion characteristics of tunicates, a series of biomimetic antibacterial hydrogels were prepared by utilizing pyrogallol-modified chitosan (GACS) and polyvinyl alcohol (PVA) as matrix, zinc ions (Zn2+) as crosslinking and antibacterial agents, and ethyl N-lauroyl l-arginate hydrochloride (LAE) as the antibacterial active ingredient. The morphology, swelling, water retention, degradability, wet adhesion, biocompatibility, mechanical and rheological properties of PVA/GACS/Zn2+/LAE hydrogels were evaluated. And the adhesion ability conferred by the pyrogallol structures enabled the hydrogel with enhanced antibacterial effect and hemostatic ability. Moreover, the in vivo experiments on rat models with full-thickness infected wounds confirmed that PVA/GACS/Zn2+/LAE hydrogels could efficiently kill bacteria, significantly improve the wound microenvironment, greatly promote fibroblast proliferation and collagen deposition and ultimately accelerate wound healing. In a word, this study provided a feasible and simple way for the development of biomimetic antibacterial hydrogel dressings applied in infected wounds, which could not only seal wounds with various shapes and provide a moist and antibacterial environment for wounds, but also have certain mechanical strength, excellent wound adhesion, good biocompatibility and hemostatic performance.