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1.
Carbohydr Polym ; 337: 122159, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710574

ABSTRACT

Chitosan and chitosan derivatives can kill pathogenic microorganisms including bacteria and fungi. The antimicrobial activity is dependent on the degree of acetylation, substituent structure, and molecular weight. Over the past four decades, numerous studies have endeavored to elucidate the relationship between molecular weight and the activity against microorganisms. However, investigators have reported divergent and, at times, conflicting conclusions. Here a bilinear equation is proposed, delineating the relationship between antimicrobial activity, defined as log (1/MIC), and the molecular weight of chitosan and chitosan derivatives. Three constants AMin, AMax, and CMW govern the shape of the curve determined by the equation. The constant AMin denotes the minimal activity expected as the molecular weight tends towards zero while AMax represents the maximal activity observed for molecular weights exceeding CMW, the critical molecular weight required for max activity. This equation was applied to analyze data from seven studies conducted between 1984 and 2019, which reported MIC (Minimum Inhibitory Concentration) values against bacteria and fungi for various molecular weights of chitosan and its derivatives. All the 29 datasets exhibited a good fit (R2 ≥ 0.5) and half excellent (R2 ≥ 0.95) fit to the equation. The CMW generally ranged from 4 to 10 KD for datasets with an excellent fit to the equation.


Subject(s)
Bacteria , Chitosan , Fungi , Microbial Sensitivity Tests , Molecular Weight , Chitosan/chemistry , Chitosan/pharmacology , Fungi/drug effects , Bacteria/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Polymers/chemistry , Polymers/pharmacology
2.
Molecules ; 29(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731481

ABSTRACT

As the use of antibiotics increases, the increasing resistance of bacteria is the main reason for the reduced efficiency of antibacterial drugs, making the research of new antibacterial materials become new hot spot. In this article, two novel coordination polymers (CPs), namely, [Cd2(L)2(bibp)2]n (1) and [Ni(L)(bib)]n (2), where H2L = N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene, bibp = 4,4'-bis(imidazol-1-yl)biphenyl, and bib = 1,3-bis(1-imidazoly)benzene, have been synthesized under solvothermal and hydrothermal condition. Structural clarification was performed through infrared spectrum and single-crystal X-ray diffraction analysis, while thermal analysis and XRD technology were used for the performance assessment of compounds 1 and 2. In addition, antibacterial performance experiments showed that compounds 1 and 2 have certain selectivity in their antibacterial properties and have good antibacterial properties against S. aureus. As the concentration of the compound increases, the inhibitory effect gradually strengthens, and when the concentration of the compound reaches 500 µg/mL and 400 µg/mL, the concentration of the S. aureus solution no longer increases and has been completely inhibited.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Polymers , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Staphylococcus aureus/drug effects , Polymers/chemistry , Polymers/pharmacology , Polymers/chemical synthesis , Ligands , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Molecular Structure , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/chemical synthesis , Models, Molecular , Crystallography, X-Ray
3.
ACS Appl Mater Interfaces ; 16(20): 25757-25772, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38738757

ABSTRACT

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.


Subject(s)
Anti-Bacterial Agents , Biofilms , Indoles , NF-kappa B , Nanoparticles , Quorum Sensing , Wound Healing , Biofilms/drug effects , Nanoparticles/chemistry , Mice , NF-kappa B/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Wound Healing/drug effects , Animals , Quorum Sensing/drug effects , Indoles/chemistry , Indoles/pharmacology , Signal Transduction/drug effects , Flavanones/chemistry , Flavanones/pharmacology , RAW 264.7 Cells , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Polymers/chemistry , Polymers/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Immunomodulating Agents/chemistry , Immunomodulating Agents/pharmacology , Humans
4.
Molecules ; 29(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38792232

ABSTRACT

Poly(2-hydroxyethylmethacrylate-co-2-(dimethylamino)ethyl methacrylate), P(HEMA-co-DMAEMAx), copolymers were quaternized through the reaction of a part of (dimethylamino)ethyl moieties of DMAEMA units with 1-bromohexadecane. Antimicrobial coatings were further prepared through the cross-linking reaction between the remaining DMAEMA units of these copolymers and the epoxide ring of poly(N,N-dimethylacrylamide-co-glycidyl methacrylate), P(DMAm-co-GMAx), copolymers. The combination of P(HEMA-co-DMAEMAx)/P(DMAm-co-GMAx) copolymers not only enabled control over quaternization and cross-linking for coating stabilization but also allowed the optimization of the processing routes towards a more facile cost-effective methodology and the use of environmentally friendly solvents like ethanol. Careful consideration was given to achieve the right content of quaternized units, qDMAEMA, to ensure antimicrobial efficacy through an appropriate amphiphilic balance and sufficient free DMAEMA groups to react with GMA for coating stabilization. Optimal synthesis conditions were achieved by membranes consisting of cross-linked P(HEMA78-co-DMAEMA9-co-qDMAEMA13)/P(DMAm-co-GMA42) membranes. The obtained membranes were multifunctional as they were self-standing and antimicrobial, while they demonstrated a distinct fast response to changes in humidity levels, widening the opportunities for the construction of "smart" antimicrobial actuators, such as non-contact antimicrobial switches.


Subject(s)
Anti-Infective Agents , Humidity , Methacrylates , Methacrylates/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Cross-Linking Reagents/chemistry , Microbial Sensitivity Tests , Polymers/chemistry , Polymers/chemical synthesis , Polymers/pharmacology
5.
Langmuir ; 40(21): 10957-10965, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38752656

ABSTRACT

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.


Subject(s)
Anti-Bacterial Agents , Polymers , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Polymers/chemistry , Polymers/pharmacology , Staphylococcus aureus/drug effects , Animals , Biofouling/prevention & control , Escherichia coli/drug effects , Bivalvia/chemistry , Surface Properties , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/chemistry , Phosphorylcholine/pharmacology , Serum Albumin, Bovine/chemistry , Humans , Methacrylates/chemistry , Methacrylates/pharmacology , Bacterial Adhesion/drug effects , Indoles
6.
ACS Appl Bio Mater ; 7(5): 2862-2871, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38699864

ABSTRACT

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.


Subject(s)
Antiviral Agents , Heparitin Sulfate , Polymers , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Heparitin Sulfate/chemistry , Heparitin Sulfate/pharmacology , Animals , Humans , Polymers/chemistry , Polymers/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Culicidae/drug effects , Culicidae/virology , Microbial Sensitivity Tests , Materials Testing , Particle Size , Cell Line , Molecular Structure , Chlorocebus aethiops , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Zika Virus/drug effects
7.
ACS Appl Bio Mater ; 7(5): 3283-3294, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38727030

ABSTRACT

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Gold , Materials Testing , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Phytic Acid , Staphylococcus aureus , Gold/chemistry , Gold/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Animals , Surface Properties , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cations/chemistry , Cations/pharmacology , Polymers/chemistry , Polymers/pharmacology , Titanium/chemistry , Titanium/pharmacology
8.
Appl Microbiol Biotechnol ; 108(1): 351, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819646

ABSTRACT

The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.


Subject(s)
Anti-Bacterial Agents , Emulsions , Escherichia coli Infections , Escherichia coli , Nanoparticles , Polymers , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Emulsions/chemistry , Polymers/chemistry , Polymers/pharmacology , Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Biological Products/chemistry , Biological Products/pharmacology
9.
Colloids Surf B Biointerfaces ; 238: 113928, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692175

ABSTRACT

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.


Subject(s)
Amyloid , Flavonoids , Muramidase , Polymers , Protein Aggregates , Muramidase/chemistry , Muramidase/metabolism , Humans , Polymers/chemistry , Polymers/pharmacology , Amyloid/chemistry , Amyloid/antagonists & inhibitors , Flavonoids/chemistry , Flavonoids/pharmacology , Protein Aggregates/drug effects , Animals , Chickens , Carbon/chemistry
10.
Int J Biol Macromol ; 269(Pt 2): 132207, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723823

ABSTRACT

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.


Subject(s)
Indoles , Metal-Organic Frameworks , Photothermal Therapy , Polymers , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Polymers/pharmacology , Humans , Animals , Mice , Photothermal Therapy/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Cell Line, Tumor , Nanoparticles/chemistry , Apoptosis/drug effects , Ferroptosis/drug effects , Tumor Microenvironment/drug effects , Combined Modality Therapy , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/chemistry , Hydrogen Peroxide/pharmacology , Imiquimod/pharmacology , Metallocenes/chemistry , Metallocenes/pharmacology
11.
J Mater Chem B ; 12(21): 5085-5097, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38713059

ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment associated with the accumulation of beta-amyloid protein (Aß). Aß activates glial cells in the brain, increasing the secretion of proinflammatory cytokines, which leads to neuroinflammation and neuronal death. Currently, there are no effective treatments that cure or stop its progression; therefore, AD is considered a global health priority. The main limitations are the low drug bioavailability and impermeability of the blood-brain barrier (BBB). Fortunately, nanomedicine has emerged as a promising field for the development of new nanosystems for the controlled and targeted delivery of drugs to the brain. Therefore, in this work, lipid-polymer hybrid nanoparticles (LPHNPs) conjugated with transferrin (Tf) to facilitate crossing the BBB and loaded with N-acetylcysteine (NAC) for its anti-inflammatory effect were synthesized, and their physicochemical characterization was carried out. Subsequently, an in vitro model involving human astrocytes derived from induced pluripotent stem cells (iPSC) from an AD-diagnosed patient was developed, which was brought to a reactive state by stimulation with lipopolysaccharides (LPSs). The cell culture was treated with either Tf-conjugated LPHNPs loaded with NAC (NAC-Tf-LPHNPs) at 0.25 mg mL-1, or free NAC at 5 mM. The results showed that NAC-Tf-LPHNPs favorably modulated the expression of proinflammatory genes such as interleukin-1ß (IL-1ß), amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP). In addition, they reduced the secretion of the proinflammatory cytokines interleukin 6 (IL-6), IL-1ß and interferon-gamma (INF-γ). Results for both cases were compared to the group of cells that did not receive any treatment. In contrast, free NAC only had this effect on the expression of IL-1ß and the secretion of the cytokines IL-6 and INF-γ. These results indicate the potential of NAC-Tf-LPHNPs for AD treatment.


Subject(s)
Acetylcysteine , Alzheimer Disease , Astrocytes , Induced Pluripotent Stem Cells , Nanoparticles , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Nanoparticles/chemistry , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/drug effects , Acetylcysteine/chemistry , Acetylcysteine/pharmacology , Astrocytes/drug effects , Astrocytes/metabolism , Polymers/chemistry , Polymers/pharmacology , Lipids/chemistry , Biomarkers/metabolism , Particle Size , Neuroinflammatory Diseases/drug therapy
12.
ChemistryOpen ; 13(5): e202300223, 2024 May.
Article in English | MEDLINE | ID: mdl-38647351

ABSTRACT

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) for the produced AgNP-decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP-decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 µg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP-decorated vesicles.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Metal Nanoparticles , Microbial Sensitivity Tests , Silver , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Humans , Cell Survival/drug effects , A549 Cells , Polymers/chemistry , Polymers/pharmacology
13.
Sci Rep ; 14(1): 8025, 2024 04 05.
Article in English | MEDLINE | ID: mdl-38580807

ABSTRACT

The modification of the surgical polypropylene mesh and the polytetrafluoroethylene vascular prosthesis with cecropin A (small peptide) and puromycin (aminonucleoside) yielded very stable preparations of modified biomaterials. The main emphasis was placed on analyses of their antimicrobial activity and potential immunomodulatory and non-cytotoxic properties towards the CCD841 CoTr model cell line. Cecropin A did not significantly affect the viability or proliferation of the CCD 841 CoTr cells, regardless of its soluble or immobilized form. In contrast, puromycin did not induce a significant decrease in the cell viability or proliferation in the immobilized form but significantly decreased cell viability and proliferation when administered in the soluble form. The covalent immobilization of these two molecules on the surface of biomaterials resulted in stable preparations that were able to inhibit the multiplication of Staphylococcus aureus and S. epidermidis strains. It was also found that the preparations induced the production of cytokines involved in antibacterial protection mechanisms and stimulated the immune response. The key regulator of this activity may be related to TLR4, a receptor recognizing bacterial LPS. In the present study, these factors were produced not only in the conditions of LPS stimulation but also in the absence of LPS, which indicates that cecropin A- and puromycin-modified biomaterials may upregulate pathways leading to humoral antibacterial immune response.


Subject(s)
Anti-Infective Agents , Biocompatible Materials , Biocompatible Materials/pharmacology , Lipopolysaccharides , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polymers/pharmacology , Staphylococcus epidermidis , Puromycin
14.
Cells ; 13(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38667271

ABSTRACT

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.


Subject(s)
Antimicrobial Peptides , Benzophenones , Polymers , Printing, Three-Dimensional , Prostheses and Implants , Staphylococcus aureus , Humans , Staphylococcus aureus/drug effects , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/metabolism , Prostheses and Implants/adverse effects , Polymers/chemistry , Polymers/pharmacology , Biofilms/drug effects , Ketones/chemistry , Ketones/pharmacology , Osteoblasts/drug effects , Osteoblasts/metabolism , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Surface Properties , Bone and Bones/drug effects , Bone and Bones/metabolism , Orthopedics
15.
Int J Biol Macromol ; 268(Pt 2): 131724, 2024 May.
Article in English | MEDLINE | ID: mdl-38653427

ABSTRACT

The emergence of novel well-defined biological macromolecular architectures containing fluorine moieties displaying superior functionalities can satisfactorily address many biomedical challenges. In this research, ABA- and AB-type glucose-based biological macromolecules were synthesized using acryl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside with pentafluorophenyl (FPM), pentafluorobenzyl (FBM), phenyl (PM) and benzyl (BM) methacrylate-based macro-RAFT agents following RAFT polymerization. The macro-RAFT agents and the corresponding copolymers were characterized by 19F, 1H, and 13C NMR and FTIR spectroscopic techniques to understand the chemical structure, molecular weight by size-exclusion chromatography, thermal analysis by TGA and DSC. Thermal stability (Td5%) of the FPM and FBM fluoro-based polymers was observed in the range of 219-267 °C, while the non-fluoro PM and BM polymers exhibited in the range of 216-264 °C. Among the macro-RAFT agents, PFPM (107 °C, ΔH: 0.613 J/g) and PPM (103 °C, ΔH: 0.455 J/g) showed higher Tm values, while among the block copolymers, PFBM-b-PG (123 °C, ΔH: 0.412 J/g) and PG-b-PFPM-b-PG (126 °C, ΔH: 0.525 J/g) exhibited higher Tm values. PFBMT and PPM macro-RAFT agents, PPM-b-PG and PG-b-PPM-b-PG copolymer spin-coated films showed the highest hydrophobicity (120°) among the synthesized polymers. The block copolymers exhibited self-assembled segregation by using relatively hydrophobic segments as the core and hydrophilic moieties as the corona. Synthesized biological macromolecules exhibit maximum antibacterial activity towards S. aureus than E. coli bacteria. Fluorophenyl (PFPM) and non-fluorobenzyl-based (PBMT) macro-RAFT agents exhibit low IC50 values, suggesting high cytotoxicity. All the triblock copolymers exhibit lesser cytotoxicity than the di-block polymers.


Subject(s)
Glucose , Macromolecular Substances , Glucose/chemistry , Macromolecular Substances/chemistry , Macromolecular Substances/chemical synthesis , Macromolecular Substances/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Polymers/chemistry , Polymers/chemical synthesis , Polymers/pharmacology , Humans , Polymerization , Molecular Weight , Fluorine/chemistry , Chemistry Techniques, Synthetic
16.
ACS Appl Mater Interfaces ; 16(19): 25194-25209, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38684227

ABSTRACT

The revolutionary self-healing function for long-term and safe service processes has inspired researchers to implement them in various fields, including in the application of antimicrobial protective coatings. Despite the great advances that have been made in the field of fabricating self-healing and antimicrobial polymers, their poor transparency and the trade-off between the mechanical and self-healing properties limit the utility of the materials as transparent antimicrobial protective coatings for wearable optical and display devices. Considering the compatibility in the blending process, our group proposed a self-healing, self-cross-linkable poly{(n-butyl acrylate)-co-[N-(hydroxymethyl)acrylamide]} copolymer (AP)-based protective coating combined with two types of commercial cationic antimicrobial agents (i.e., dimethyl octadecyl (3-trimethoxysilylpropyl) ammonium chloride (DTSACL) and chlorhexidine gluconate (CHG)), leading to the fabrication of a multifunctional modified compound film of (AP/b%CHG)-grafted-a%DTSACL. The first highlight of this research is that the reactivity of the hydroxyl group in the N-(hydroxymethyl)acrylamide of the copolymer side chains under thermal conditions facilitates the "grafting to" process with the trimethoxysilane groups of DTSACL to form AP-grafted-DTSACL, yielding favorable thermal stability, improvement in hydrophobicity, and enhancement of mechanical strength. Second, we highlight that the addition of CHG can generate covalent and noncovalent interactions in a complex manner between the two biguanide groups of CHG with the AP and DTSACL via a thermal-triggered cross-linking reaction. The noncovalent interactions synergistically serve as diverse dynamic hydrogen bonds, leading to complete healing upon scratches and even showing over 80% self-healing efficiency on full-cut, while covalent bonding can effectively improve elasticity and mechanical strength. The soft nature of CHG also takes part in improving the self-healing of the copolymer. Moreover, it was discovered that the addition of CHG can enhance antimicrobial effectiveness, as demonstrated by the long-term superior antibacterial activity (100%) against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and the antifouling function on a glass substrate and/or a silica wafer coated by the modified polymer.


Subject(s)
Polymers , Polymers/chemistry , Polymers/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Elasticity , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chlorhexidine/chemistry , Chlorhexidine/pharmacology , Chlorhexidine/analogs & derivatives
17.
Nanotechnology ; 35(32)2024 May 21.
Article in English | MEDLINE | ID: mdl-38688249

ABSTRACT

Dealing with bone defects is a significant challenge to global health. Electrospinning in bone tissue engineering has emerged as a solution to this problem. In this study, we designed a PVDF-b-PTFE block copolymer by incorporating TFE, which induced a phase shift in PVDF fromαtoß, thereby enhancing the piezoelectric effect. Utilizing the electrospinning process, we not only converted the material into a film with a significant surface area and high porosity but also intensified the piezoelectric effect. Then we used polydopamine to immobilize BMP-2 onto PVDF-b-PTFE electrospun nanofibrous membranes, achieving a controlled release of BMP-2. The scaffold's characters were examined using SEM and XRD. To assess its osteogenic effectsin vitro, we monitored the proliferation of MC3T3-E1 cells on the fibers, conducted ARS staining, and measured the expression of osteogenic genes.In vivo, bone regeneration effects were analyzed through micro-CT scanning and HE staining. ELISA assays confirmed that the sustained release of BMP-2 can be maintained for at least 28 d. SEM images and CCK-8 results demonstrated enhanced cell viability and improved adhesion in the experimental group. Furthermore, the experimental group exhibited more calcium nodules and higher expression levels of osteogenic genes, including COL-I, OCN, and RUNX2. HE staining and micro-CT scans revealed enhanced bone tissue regeneration in the defective area of the PDB group. Through extensive experimentation, we evaluated the scaffold's effectiveness in augmenting osteoblast proliferation and differentiation. This study emphasized the potential of piezoelectric PVDF-b-PTFE nanofibrous membranes with controlled BMP-2 release as a promising approach for bone tissue engineering, providing a viable solution for addressing bone defects.


Subject(s)
Bone Morphogenetic Protein 2 , Bone Regeneration , Indoles , Nanofibers , Osteogenesis , Polymers , Tissue Engineering , Tissue Scaffolds , Bone Morphogenetic Protein 2/pharmacology , Bone Morphogenetic Protein 2/metabolism , Nanofibers/chemistry , Bone Regeneration/drug effects , Animals , Mice , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Polymers/pharmacology , Tissue Engineering/methods , Osteogenesis/drug effects , Tissue Scaffolds/chemistry , Cell Proliferation/drug effects , Cell Line , Immobilized Proteins/pharmacology , Immobilized Proteins/chemistry , Cell Survival/drug effects
18.
ACS Appl Bio Mater ; 7(5): 2851-2861, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38587870

ABSTRACT

Periodontitis is a chronic oral inflammatory disease with the characteristic of excess oxidative stress in the inflammatory site, dramatically decreasing the quality of life. Studies show that nanozymes can be ideal candidates for ROS scavenging in periodontitis. Here, we design a multipath anti-inflammatory mesoporous polydopamine@cerium oxide nanobowl (mPDA@CeO2 NB) with multienzyme mimicking properties, which combines the advantages of both CeO2 NP and mPDA NB for synergistically eliminating reactive oxygen species (ROS), including hydroxyl radical (•OH), hydrogen peroxide (H2O2), and superoxide (O2•-). Besides, the erythrocyte-like structure of mNBs makes them a facility for cell uptake, and the mesopores can load both hydrophobic and hydrophilic drugs for combined anti-inflammatory therapy. In vitro and in vivo experiments prove that the combination of CeO2 and mPDA can synergistically achieve multiple complementary ROS eliminations and suppression of ROS-induced inflammation. Moreover, the ROS regulation plus anti-inflammatory drugs in one mPDA@CeO2 NB prevents the progression of periodontitis in a mouse model. Therefore, the design of mPDA@CeO2 NB with these excellent properties provides a therapeutic strategy for inflammatory diseases.


Subject(s)
Cerium , Indoles , Materials Testing , Particle Size , Periodontitis , Polymers , Cerium/chemistry , Cerium/pharmacology , Periodontitis/drug therapy , Animals , Mice , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Polymers/pharmacology , Reactive Oxygen Species/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Porosity , Erythrocytes/drug effects , Erythrocytes/metabolism , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
19.
ACS Appl Bio Mater ; 7(5): 3469-3482, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38651365

ABSTRACT

Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.


Subject(s)
Anti-Bacterial Agents , Biocompatible Materials , Carboxymethylcellulose Sodium , Escherichia coli , Gelatin , Hydrogels , Materials Testing , Microbial Sensitivity Tests , Wound Healing , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Gelatin/chemistry , Wound Healing/drug effects , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Escherichia coli/drug effects , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Mice , Staphylococcus aureus/drug effects , Particle Size , Methicillin-Resistant Staphylococcus aureus/drug effects , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Indoles/pharmacology , Copper/chemistry , Copper/pharmacology , Humans
20.
ACS Appl Bio Mater ; 7(5): 2966-2981, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38652577

ABSTRACT

This study presents a facile fabrication of 58S bioactive glass (BG)-polymer composite coatings on a 316L stainless steel (SS) substrate using the electrophoretic deposition technique. The suspension characteristics and deposition kinetics of BG, along with three different polymers, namely ethylcellulose (EC), poly(acrylic acid) (PAA), and polyvinylpyrrolidone (PVP), have been utilized to fabricate the coatings. Among all coatings, 58S BG and EC polymers are selected as the final composite coating (EC6) owing to their homogeneity and good adhesion. EC6 coating exhibits a thickness of ∼18 µm and an average roughness of ∼2.5 µm. Herein, EC6 demonstrates better hydroxyapatite formation compared to PAA and PVP coatings in simulated body fluid-based mineralization studies for a period of 28 days. Corrosion studies of EC6 in phosphate-buffered saline further confirm the higher corrosion resistance properties after 14 days. In vitro cytocompatibility studies using human placental mesenchymal stem cells demonstrate an increase in cellular viability, attachment, and higher proliferation compared to the bare SS substrate. EC6 coatings promote osteogenic differentiation, which is confirmed via the upregulation of the OPN and OCN genes. Moreover, the EC6 sample exhibits improved antibacterial properties against Escherichia coli and Staphylococcus aureus compared to the uncoated ones. The findings of this work emphasize the potential of electrophoretically fabricated BG-EC composite coatings on SS substrates for orthopedic applications.


Subject(s)
Coated Materials, Biocompatible , Glass , Materials Testing , Polymers , Stainless Steel , Stainless Steel/chemistry , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Glass/chemistry , Polymers/chemistry , Polymers/pharmacology , Corrosion , Particle Size , Surface Properties , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Electrophoresis , Cell Survival/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Microbial Sensitivity Tests , Cell Proliferation/drug effects
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