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Keywords = covalent antibacterial conjugate

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24 pages, 6370 KiB  
Article
Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity
by Carolina Silva Ferreira, Lívia Mara Fontes Costa, Lúcio Otávio Nunes, Kelton Rodrigues de Souza, Giovanna Paula Araújo, Evgeniy S. Salnikov, Kelly Cristina Kato, Helen Rodrigues Martins, Adriano Monteiro de Castro Pimenta, Jarbas Magalhães Resende, Burkhard Bechinger and Rodrigo Moreira Verly
Pharmaceuticals 2025, 18(7), 952; https://doi.org/10.3390/ph18070952 - 24 Jun 2025
Viewed by 506
Abstract
Background/Objectives: The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. [...] Read more.
Background/Objectives: The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. The main objective was to investigate how the site of peptide functionalization (C-terminal vs. N-terminal) affects membrane interactions and antibacterial activity. Methods: NP–peptide conjugates were synthesized via covalent bonding between lun-1 and alumina NP and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and solid-state 13C NMR. Antibacterial activities were assessed against different Gram-positive and Gram-negative strains. Biophysical analyses, including circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and solid-state 2H NMR, were employed to evaluate peptide–membrane interactions in the presence of membrane-mimetic vesicles composed of POPC:POPG (3:1) and DMPC:DMPG (3:1). Results: Characterization confirmed the successful formation of NP–peptide nanofilaments. Functionalization at the N-terminal significantly influenced both antibacterial activity and peptide conformation compared to C-terminal attachment. Biophysical data demonstrated stronger membrane interaction and greater membrane disruption when lun-1 was conjugated at the N-terminal. Conclusions: The site of peptide conjugation plays a crucial role in modulating the biological and biophysical properties of NP–lunatin-1 conjugates. C-terminal attachment of lunatin-1 retains both membrane interaction and antibacterial efficacy, making it a promising strategy for the design of peptide-based nanotherapeutics targeting resistant pathogens. Full article
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16 pages, 2632 KiB  
Article
Rose Bengal Conjugated to Lectins for Targeted Antibacterial Photodynamic Treatment
by Melad Atrash, Iryna Hovor, Marina Nisnevitch and Faina Nakonechny
Molecules 2025, 30(11), 2381; https://doi.org/10.3390/molecules30112381 - 29 May 2025
Viewed by 588
Abstract
Due to rising antibiotic resistance, it is necessary to develop alternative ways to combat pathogenic bacteria. One alternative is photodynamic antibacterial chemotherapy (PACT). This work presents the conjugation of the photosensitizer Rose Bengal (RB) to lectins to improve its efficacy against Gram-positive and [...] Read more.
Due to rising antibiotic resistance, it is necessary to develop alternative ways to combat pathogenic bacteria. One alternative is photodynamic antibacterial chemotherapy (PACT). This work presents the conjugation of the photosensitizer Rose Bengal (RB) to lectins to improve its efficacy against Gram-positive and Gram-negative bacteria. Two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), were covalently linked to RB. Spectroscopic and chromatographic data confirmed successful conjugation. Microscopic examination demonstrated that both lectins agglutinate cells of Gram-positive S. aureus, including clinical multidrug-resistant MRSA strains, and Gram-negative E. coli, P. aeruginosa, and S. paratyphi B, although ConA showed a more pronounced reaction. Photodynamic assays showed that ConA-RB achieved complete eradication of S. aureus at significantly lower concentrations and light doses than free RB or WGA-RB. ConA-RB also exhibited higher efficacy against Gram-negative bacteria compared to free RB at lower concentrations and shorter illumination periods. WGA-RB was less effective, showing preferential activity against S. aureus. Our findings suggest that lectin–RB conjugates offer a promising approach for selective antibacterial treatment under illumination. Full article
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11 pages, 799 KiB  
Article
Impact of Hydrophobic, Hydrophilic, and Mucus-Binding Motifs on the Therapeutic Potential of Ceftazidime Analogs for Pulmonary Administration
by Kyle D. Apley, Stephanie N. Johnson, Jian Qian, Indeewara Munasinghe, Jennifer R. Klaus, Srilaxmi M. Patel, Kathryn E. Woods, Samalee Banerjee, Josephine R. Chandler, Chamani Perera, Nathalie Baumlin, Matthias Salathe and Cory J. Berkland
Antibiotics 2025, 14(2), 177; https://doi.org/10.3390/antibiotics14020177 - 11 Feb 2025
Viewed by 1607
Abstract
Background/Objectives: The pulmonary administration of antibiotics can be advantageous in treating pulmonary infections by promoting high intrapulmonary drug concentrations with reduced systemic exposure. However, limited benefits have been observed for pulmonary administration versus other administration routes due to its rapid clearance from [...] Read more.
Background/Objectives: The pulmonary administration of antibiotics can be advantageous in treating pulmonary infections by promoting high intrapulmonary drug concentrations with reduced systemic exposure. However, limited benefits have been observed for pulmonary administration versus other administration routes due to its rapid clearance from the lung. Here, the effects of structural modifications on the epithelial permeability and antibacterial potency of a third-generation cephalosporin were investigated to improve the understanding of drug properties that promote intrapulmonary retention and how they may impact efficacy. Methods: Ceftazidime was modified by attaching 18 hydrophobic, hydrophilic, and mucus-binding motifs to the carboxylic acid distant from the beta-lactam by amidation. Epithelial permeability was investigated by drug transport assays using human bronchial epithelial air–liquid interface cultures. Antibacterial potency was determined by microtiter MIC assays with B. pseudomallei, P. aeruginosa, E. coli, and S. aureus. Results: A 40–50% reduction in the transepithelial transport rate was exhibited by two PEGylated ceftazidime analogs (mPEG8- and PEG5-pyrimidin-2-amine-ceftazidime) and n-butyl-ceftazidime. An increase in the transport rate was exhibited by four analogs bearing small and hydrophobic or negatively charged motifs (n-heptane-, phenyl ethyl-, glutamic acid-, and 4-propylthiophenyl boronic acid-ceftazidime). The antibacterial potency was reduced by ≥10-fold for most ceftazidime analogs against B. pseudomallei, P. aeruginosa, and E. coli but was retained by seven ceftazidime analogs primarily bearing hydrophobic motifs against S. aureus. Conclusions: The covalent conjugation of PEGs with MW > 300 Da reduced the epithelial permeability of ceftazidime, but these modifications severely reduced antibacterial activity. To improve the pulmonary retention of antibiotics with low membrane permeability, this work suggests future molecular engineering studies to explore high-molecular-weight prodrug strategies. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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21 pages, 12533 KiB  
Review
Recent Advances in Porphyrin-Based Covalent Organic Frameworks for Synergistic Photodynamic and Photothermal Therapy
by Cheng Qi, Jiayi Chen, Yijie Qu, Xuanxuan Luo, Weiqi Wang and Xiaohua Zheng
Pharmaceutics 2024, 16(12), 1625; https://doi.org/10.3390/pharmaceutics16121625 - 22 Dec 2024
Cited by 3 | Viewed by 1904
Abstract
Porphyrin’s excellent biocompatibility and modifiability make it a widely studied photoactive material. However, its large π-bond conjugated structure leads to aggregation and precipitation in physiological solutions, limiting the biomedical applications of porphyrin-based photoactive materials. It has been demonstrated through research that fabricating porphyrin [...] Read more.
Porphyrin’s excellent biocompatibility and modifiability make it a widely studied photoactive material. However, its large π-bond conjugated structure leads to aggregation and precipitation in physiological solutions, limiting the biomedical applications of porphyrin-based photoactive materials. It has been demonstrated through research that fabricating porphyrin molecules into nanoscale covalent organic frameworks (COFs) structures can circumvent issues such as poor dispersibility resulting from hydrophobicity, thereby significantly augmenting the photoactivity of porphyrin materials. Porphyrin-based COF materials can exert combined photodynamic and photothermal effects, circumventing the limitations of photodynamic therapy (PDT) due to hypoxia and issues in photothermal therapy (PTT) from heat shock proteins or the adverse impact of excessive heat on the protein activity of normal tissue. Furthermore, the porous structure of porphyrin COFs facilitates the circulation of oxygen molecules and reactive oxygen species and promotes sufficient contact with the lesion site for therapeutic functions. This review covers recent progress regarding porphyrin-based COFs in treating malignant tumors and venous thrombosis and for antibacterial and anti-inflammatory uses via combined PDT and PTT. By summarizing relevant design strategies, ranging from molecular design to functional application, this review provides a reference basis for the enhanced phototherapy application of porphyrin-based COFs as photoactive materials. This review aims to offer valuable insights for more effective biomedical applications of porphyrin-based COFs through the synthesis of existing experimental data, thereby paving the way for their future preclinical utilization. Full article
(This article belongs to the Special Issue Advanced Nanotechnology for Combination Therapy and Diagnosis)
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31 pages, 2559 KiB  
Review
Origami of KR-12 Designed Antimicrobial Peptides and Their Potential Applications
by Jayaram Lakshmaiah Narayana, Abraham Fikru Mechesso, Imran Ibni Gani Rather, D. Zarena, Jinghui Luo, Jingwei Xie and Guangshun Wang
Antibiotics 2024, 13(9), 816; https://doi.org/10.3390/antibiotics13090816 - 28 Aug 2024
Cited by 4 | Viewed by 3631
Abstract
This review describes the discovery, structure, activity, engineered constructs, and applications of KR-12, the smallest antibacterial peptide of human cathelicidin LL-37, the production of which can be induced under sunlight or by vitamin D. It is a moonlighting peptide that shows both antimicrobial [...] Read more.
This review describes the discovery, structure, activity, engineered constructs, and applications of KR-12, the smallest antibacterial peptide of human cathelicidin LL-37, the production of which can be induced under sunlight or by vitamin D. It is a moonlighting peptide that shows both antimicrobial and immune-regulatory effects. Compared to LL-37, KR-12 is extremely appealing due to its small size, lack of toxicity, and narrow-spectrum antimicrobial activity. Consequently, various KR-12 peptides have been engineered to tune peptide activity and stability via amino acid substitution, end capping, hybridization, conjugation, sidechain stapling, and backbone macrocyclization. We also mention recently discovered peptides KR-8 and RIK-10 that are shorter than KR-12. Nano-formulation provides an avenue to targeted delivery, controlled release, and increased bioavailability. In addition, KR-12 has been covalently immobilized on biomaterials/medical implants to prevent biofilm formation. These constructs with enhanced potency and stability are demonstrated to eradicate drug-resistant pathogens, disrupt preformed biofilms, neutralize endotoxins, and regulate host immune responses. Also highlighted are the safety and efficacy of these peptides in various topical and systemic animal models. Finaly, we summarize the achievements and discuss future developments of KR-12 peptides as cosmetic preservatives, novel antibiotics, anti-inflammatory peptides, and microbiota-restoring agents. Full article
(This article belongs to the Special Issue Insights into Natural Antimicrobial Peptides)
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37 pages, 9611 KiB  
Review
Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic–Antimicrobial Peptide Conjugates
by Maria Cristina Bellucci, Carola Romani, Monica Sani and Alessandro Volonterio
Antibiotics 2024, 13(8), 783; https://doi.org/10.3390/antibiotics13080783 - 21 Aug 2024
Cited by 7 | Viewed by 2710
Abstract
In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective [...] Read more.
In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity. Full article
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23 pages, 3043 KiB  
Article
Maleic Anhydride-Derived Copolymers Conjugated with Beta-Lactam Antibiotics: Synthesis, Characterization, In Vitro Activity/Stability Tests with Antibacterial Studies
by Aysegul Kahraman, Dolunay Sakar and Melda Altikatoglu Yapaoz
Appl. Sci. 2024, 14(14), 6112; https://doi.org/10.3390/app14146112 - 13 Jul 2024
Viewed by 1426
Abstract
The synthesis and characterization of biocompatible three different maleic anhydride co-polymer conjugated with two different beta-lactam antibiotics at in vitro conditions were conducted. The polymer–drug conjugates were synthesized by coupling β-lactam antibiotics via amide bonds to the copolymer. In this work, six different [...] Read more.
The synthesis and characterization of biocompatible three different maleic anhydride co-polymer conjugated with two different beta-lactam antibiotics at in vitro conditions were conducted. The polymer–drug conjugates were synthesized by coupling β-lactam antibiotics via amide bonds to the copolymer. In this work, six different drug-functionalized maleic anhydride copolymers (DFMACs) were synthesized by the chemical conjugation method. This method is based on the ring-opening reaction of the anhydride ring of the copolymer to form an amide bond linking the drug. The synthesized DFMACs were characterized by 1H NMR and FTIR/ATR spectroscopies and analyses were carried out by UV/VIS spectroscopy and Zeta-sizer instrument in detail with consecutive antibacterial tests. The existence of a newly formed amide covalent bond between the drug and the copolymer chains was confirmed by 1H NMR and FTIR/ATR studies. This is the first report on the application of the selected branched biodegradable polymeric matrices for the covalent conjugation of ampicillin and cefalexin. Optimum stability and activity conditions for the synthesized DFMACs were determined. Analyses were conducted under in vitro conditions including varying pH values and simulated body fluids as a function of time to obtain new drug delivery system candidates for the two different antibiotics. Full article
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22 pages, 2785 KiB  
Article
Comparison of Non-Covalent and Covalent Interactions between Lactoferrin and Chlorogenic Acid
by Zekun Li, Majida Al-Wraikat, Changchun Hao and Yongfeng Liu
Foods 2024, 13(8), 1245; https://doi.org/10.3390/foods13081245 - 19 Apr 2024
Cited by 9 | Viewed by 2575
Abstract
Adding polyphenols to improve the absorption of functional proteins has become a hot topic. Chlorogenic acid is a natural plant polyphenol with anti-inflammatory, antioxidant, and anticancer properties. Bovine lactoferrin is known for its immunomodulatory, anticancer, antibacterial, and iron-chelating properties. Therefore, the non-covalent binding [...] Read more.
Adding polyphenols to improve the absorption of functional proteins has become a hot topic. Chlorogenic acid is a natural plant polyphenol with anti-inflammatory, antioxidant, and anticancer properties. Bovine lactoferrin is known for its immunomodulatory, anticancer, antibacterial, and iron-chelating properties. Therefore, the non-covalent binding of chlorogenic acid (CA) and bovine lactoferrin (BLF) with different concentrations under neutral conditions was studied. CA was grafted onto lactoferrin molecules by laccase catalysis, free radical grafting, and alkali treatment. The formation mechanism of non-covalent and covalent complexes of CA-BLF was analyzed by experimental test and theoretical prediction. Compared with the control BLF, the secondary structure of BLF in the non-covalent complex was rearranged and unfolded to provide more active sites, the tertiary structure of the covalent conjugate was changed, and the amino group of the protein participated in the covalent reaction. After adding CA, the covalent conjugates have better functional activity. These lactoferrin–polyphenol couplings can carry various bioactive compounds to create milk-based delivery systems for encapsulation. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
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32 pages, 13639 KiB  
Article
Covalent Conjugates of Allylbenzenes and Terpenoids as Antibiotics Enhancers with the Function of Prolonged Action
by Igor D. Zlotnikov, Maria P. Davydova, Milan R. Danilov, Sergey S. Krylov, Natalya G. Belogurova and Elena V. Kudryashova
Pharmaceuticals 2023, 16(8), 1102; https://doi.org/10.3390/ph16081102 - 4 Aug 2023
Cited by 5 | Viewed by 1867
Abstract
The drug resistance of pathogenic bacteria is often due efflux pumps—specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the [...] Read more.
The drug resistance of pathogenic bacteria is often due efflux pumps—specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the action of antibiotics. We assumed that a new level of effectiveness with the use of an antibiotic + an adjuvant pair could be achieved by their joint delivery into the pathogen. To test this hypothesis, we constructed a series of molecular carriers based on poly-(olygo-, dendry)mers based on cyclodextrin-grafted PEI or mannan, as well as glycol chitosan, covalently bound to antibiotic, adjuvant, and the oligosaccharide ligand to the macrophage mannose receptor (CD206), which we studied earlier and showed high efficiency and selectivity of delivery of a therapeutic “cargo” to macrophages. Moxifloxacin was used as an antibiotic, and terpenoid and allylbenzene compounds were used as adjuvants, for which we previously discovered the ability to inhibit bacterial efflux pumps. We show that: (a) the resulting structures were stable in vitro for a long time (up to 10 days); (b) they were adsorbed on bacterial cells, providing a local increase in the concentration of the antibiotic and adjuvant in pathogen cells; (c) they were internalized by bacterial cells, ensuring the accumulation of both antibiotic and adjuvant inside bacterial cells; (d) the adjuvant, after entering the bacterial cell, provided inhibition of the efflux pumps; (e) due to this action of the adjuvant, combined with the targeted delivery by the carrier, the antibiotic’s half-life in rats increased by more than 2 times, the effective concentration of the drug in the blood plasma (AUC) increased up to 8–10 times; (f) a significant increase in the effectiveness of the antibacterial action against Gram+ and Gram- cells was achieved (up to 3 times). Potentially, such an approach would significantly increase the effectiveness of therapies for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing bacterial resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures will avoid problems linked to different (suboptimal) solubility and bio-distribution of the administered molecules, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds, and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors. Full article
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17 pages, 2360 KiB  
Article
Combined System for the Simultaneous Delivery of Levofloxacin and Rifampicin: Structural and Functional Properties and Antibacterial Activity
by Irina M. Le-Deygen, Polina V. Mamaeva, Anna A. Skuredina, Anastasia S. Safronova, Natalia G. Belogurova and Elena V. Kudryashova
J. Funct. Biomater. 2023, 14(7), 381; https://doi.org/10.3390/jfb14070381 - 20 Jul 2023
Cited by 3 | Viewed by 2025
Abstract
The therapy of resistant forms of tuberculosis requires the simultaneous use of several drugs, in particular, a combination of rifampicin and levofloxacin. In this paper, we aimed to design a combined system for the simultaneous delivery of these drugs for potential inhalation administration. [...] Read more.
The therapy of resistant forms of tuberculosis requires the simultaneous use of several drugs, in particular, a combination of rifampicin and levofloxacin. In this paper, we aimed to design a combined system for the simultaneous delivery of these drugs for potential inhalation administration. A feature of this system is the incorporation of rifampicin into optimized liposomal vesicles capable of forming a multipoint non-covalent complex with chitosan-β-cyclodextrin conjugates. Levofloxacin is incorporated into cyclodextrin tori by forming a host–guest complex. Here, a comprehensive study of the physicochemical properties of the obtained systems was carried out and special attention was paid to the kinetics of cargo release for individual drugs and in the combined system. The release of levofloxacin in combined system is slow and is described by the Higuchi model in all cases. The release of rifampicin from liposomes during the formation of complexes with polymeric conjugates is characterized by the change of the Higuchi model to the Korsmeyer–Peppas model with the main type of diffusion against Fick′s law. Microbiological studies in solid and liquid growth media a consistently high antibacterial activity of the obtained systems was shown against B. subtilis and E. coli. Full article
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19 pages, 3908 KiB  
Article
Influence of Immobilization Strategies on the Antibacterial Properties of Antimicrobial Peptide-Chitosan Coatings
by Mariana Barbosa, Pedro M. Alves, Fabíola Costa, Cláudia Monteiro, Paula Parreira, Cátia Teixeira, Paula Gomes and Maria Cristina L. Martins
Pharmaceutics 2023, 15(5), 1510; https://doi.org/10.3390/pharmaceutics15051510 - 16 May 2023
Cited by 5 | Viewed by 2788
Abstract
It is key to fight bacterial adhesion to prevent biofilm establishment on biomaterials. Surface immobilization of antimicrobial peptides (AMP) is a promising strategy to avoid bacterial colonization. This work aimed to investigate whether the direct surface immobilization of Dhvar5, an AMP with head-to-tail [...] Read more.
It is key to fight bacterial adhesion to prevent biofilm establishment on biomaterials. Surface immobilization of antimicrobial peptides (AMP) is a promising strategy to avoid bacterial colonization. This work aimed to investigate whether the direct surface immobilization of Dhvar5, an AMP with head-to-tail amphipathicity, would improve the antimicrobial activity of chitosan ultrathin coatings. The peptide was grafted by copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry by either its C- or N- terminus to assess the influence of peptide orientation on surface properties and antimicrobial activity. These features were compared with those of coatings fabricated using previously described Dhvar5-chitosan conjugates (immobilized in bulk). The peptide was chemoselectively immobilized onto the coating by both termini. Moreover, the covalent immobilization of Dhvar5 by either terminus enhanced the antimicrobial effect of the chitosan coating by decreasing colonization by both Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Relevantly, the antimicrobial performance of the surface on Gram-positive bacteria depended on how Dhvar5-chitosan coatings were produced. An antiadhesive effect was observed when the peptide was grafted onto prefabricated chitosan coatings (film), and a bactericidal effect was exhibited when coatings were prepared from Dhvar5-chitosan conjugates (bulk). This antiadhesive effect was not due to changes in surface wettability or protein adsorption but rather depended on variations in peptide concentration, exposure, and surface roughness. Results reported in this study show that the antibacterial potency and effect of immobilized AMP vary greatly with the immobilization procedure. Overall, independently of the fabrication protocol and mechanism of action, Dhvar5-chitosan coatings are a promising strategy for the development of antimicrobial medical devices, either as an antiadhesive or contact-killing surface. Full article
(This article belongs to the Special Issue Antimicrobial Peptides and Antimicrobial Nanomaterials in Biomedicine)
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10 pages, 3302 KiB  
Communication
Xylan–Porphyrin Hydrogels as Light-Triggered Gram-Positive Antibacterial Agents
by Abdechakour Elkihel, Charlotte Vernisse, Tan-Sothéa Ouk, Romain Lucas-Roper, Vincent Chaleix and Vincent Sol
Gels 2023, 9(2), 124; https://doi.org/10.3390/gels9020124 - 2 Feb 2023
Cited by 3 | Viewed by 2094
Abstract
In the present work, we report on the synthesis of light-triggered antibacterial hydrogels, based on xylan chains covalently bound to meso-tetra(4-carboxyphenyl)porphyrin (TCPP). Not only does TCPP act as a photosensitizer efficient against Gram-positive bacteria, but it also serves as a cross-linking gelator, enabling [...] Read more.
In the present work, we report on the synthesis of light-triggered antibacterial hydrogels, based on xylan chains covalently bound to meso-tetra(4-carboxyphenyl)porphyrin (TCPP). Not only does TCPP act as a photosensitizer efficient against Gram-positive bacteria, but it also serves as a cross-linking gelator, enabling the simple and easy building of xylan conjugate hydrogels. The hydrogels were characterized by infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), along with swelling and rheological tests. The antimicrobial activity of the hydrogels was tested under visible light irradiation against two Gram-positive bacterial strains, Staphylococcus aureus and Bacillus cereus. The preliminary results showed an interesting activity on these bacteria, indicating that these hydrogels could be of great potential in the treatment of skin bacterial infections with this species by photodynamic antimicrobial chemotherapy (PACT). Full article
(This article belongs to the Special Issue Smart Hydrogels: From Rational Design to Applications)
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27 pages, 9418 KiB  
Article
Mannosylated Systems for Targeted Delivery of Antibacterial Drugs to Activated Macrophages
by Igor D. Zlotnikov, Maksim A. Vigovskiy, Maria P. Davydova, Milan R. Danilov, Uliana D. Dyachkova, Olga A. Grigorieva and Elena V. Kudryashova
Int. J. Mol. Sci. 2022, 23(24), 16144; https://doi.org/10.3390/ijms232416144 - 18 Dec 2022
Cited by 20 | Viewed by 3224
Abstract
Macrophages are a promising target for drug delivery to influence macrophage-associated processes in the body, namely due to the presence of resistant microorganisms in macrophages. In this work, a series of mannosylated carriers based on mannan, polyethylenimine (PEI) and cyclodextrin (CD) was synthesized. [...] Read more.
Macrophages are a promising target for drug delivery to influence macrophage-associated processes in the body, namely due to the presence of resistant microorganisms in macrophages. In this work, a series of mannosylated carriers based on mannan, polyethylenimine (PEI) and cyclodextrin (CD) was synthesized. The molecular architecture was studied using FTIR and 1H NMR spectroscopy. The particle size, from small 10–50 nm to large 500 nm, depending on the type of carrier, is potentially applicable for the creation of various medicinal forms: intravenous, oral and inhalation. Non-specific capture by cells with a simultaneous increase in selectivity to CD206+ macrophages was achieved. ConA was used as a model mannose receptor, binding galactosylated (CD206 non-specific) carriers with constants of the order of 104 M−1 and mannosylated conjugates of 106–107 M−1. The results of such primary “ConA-screening” of ligands are in a good agreement in terms of the comparative effectiveness of the interaction of ligands with the CD206+ macrophages: non-specific (up to 10%) absorption of highly charged and small particles; weakly specific uptake of galactosylated polymers (up to 50%); and high affine capture (more than 70–80%) of the ligands with grafted trimannoside was demonstrated using the cytometry method. Double and multi-complexes of antibacterials (moxifloxacin with its adjuvants from the class of terpenoids) were proposed as enhanced forms against resistant pathogens. In vivo pharmacokinetic experiments have shown that polymeric carriers significantly improve the efficiency of the antibiotic: the half-life of moxifloxacin is increased by 2–3 times in conjugate-loaded forms, bio-distribution to the lungs in the first hours after administration of the drug is noticeably greater, and, after 4 h of observation, free moxifloxacin was practically removed from the lungs of rats. Although, in polymer systems, its content is significant—1.2 µg/g. Moreover, the importance of the covalent crosslinking carrier with mannose label was demonstrated. Thus, this paper describes experimental, scientifically based methods of targeted drug delivery to macrophages to create enhanced medicinal forms. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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16 pages, 3652 KiB  
Article
The Barrier-Enhancing Function of Soluble Yam (Dioscorea opposita Thunb.) Polysaccharides in Rat Intestinal Epithelial Cells as Affected by the Covalent Se Conjugation
by Zhen-Xing Wang and Xin-Huai Zhao
Nutrients 2022, 14(19), 3950; https://doi.org/10.3390/nu14193950 - 23 Sep 2022
Cited by 11 | Viewed by 2174
Abstract
The non-starch yam polysaccharides (YP) are the bioactive substances of edible yam, while Se is an essential nutrient for the human body. Whether a covalent conjugation of Se to YP might cause bioactivity change for the resultant selenylated YP in the intestine is [...] Read more.
The non-starch yam polysaccharides (YP) are the bioactive substances of edible yam, while Se is an essential nutrient for the human body. Whether a covalent conjugation of Se to YP might cause bioactivity change for the resultant selenylated YP in the intestine is still insufficiently studied, including the critical intestinal barrier function. In this study, two selenylated YP products, namely, YPSe-I and YPSe-II, with corresponding Se contents of 795 and 1480 mg/kg, were obtained by the reaction of YP and Na2SeO3 in the presence of HNO3 and then assessed for their bioactivities to a cell model (i.e., rat intestinal epithelial IEC-6 cells). The results showed that YP, YPSe-I, and YPSe-II at 5–80 μg/mL dosages could promote cell growth with treatment times of 12–24 h. The three samples also could improve barrier integrity via increasing cell monolayer resistance and anti-bacterial activity against E. coli or by reducing paracellular permeability and bacterial translocation. Additionally, the three samples enhanced F-actin distribution and promoted the expression of the three tight junction proteins, namely, zonula occluden-1, occludin, and claudin-1. Meanwhile, the expression levels of ROCK and RhoA, two critical proteins in the ROCK/RhoA singling pathway, were down-regulated by these samples. Collectively, YPSe-I and, especially, YPSe-II were more potent than YP in enhancing the assessed bioactivities. It is thus concluded that this chemical selenylation of YP brought about enhanced activity in the cells to promote barrier integrity, while a higher selenylation extent of the selenylated YP induced much activity enhancement. Collectively, the results highlighted the important role of the non-metal nutrient Se in the modified polysaccharides. Full article
(This article belongs to the Section Micronutrients and Human Health)
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17 pages, 3422 KiB  
Article
Diamond Nanoparticles-Porphyrin mTHPP Conjugate as Photosensitizing Platform: Cytotoxicity and Antibacterial Activity
by Carolina Ramos Hurtado, Gabriela Ramos Hurtado, Gabrielle Lupeti de Cena, Rafaela Campos Queiroz, Alexandre Vieira Silva, Milton Faria Diniz, Verônica Ribeiro dos Santos, Vladimir Trava-Airoldi, Maurício da Silva Baptista, Ncediwe Tsolekile, Oluwatobi Samuel Oluwafemi, Katia Conceição and Dayane Batista Tada
Nanomaterials 2021, 11(6), 1393; https://doi.org/10.3390/nano11061393 - 25 May 2021
Cited by 13 | Viewed by 3624
Abstract
Conjugation of photosensitizers (PS) with nanoparticles has been largely used as a strategy to stabilize PS in the biological medium resulting in photosensitizing nanoparticles of enhanced photoactivity. Herein, (Meso-5, 10, 15, 20-tetrakis (3-hydroxyphenyl) phorphyryn (mTHPP) was conjugated with diamond nanoparticles (ND) by covalent [...] Read more.
Conjugation of photosensitizers (PS) with nanoparticles has been largely used as a strategy to stabilize PS in the biological medium resulting in photosensitizing nanoparticles of enhanced photoactivity. Herein, (Meso-5, 10, 15, 20-tetrakis (3-hydroxyphenyl) phorphyryn (mTHPP) was conjugated with diamond nanoparticles (ND) by covalent bond. Nanoconjugate ND-mTHPP showed suitable stability in aqueous suspension with 58 nm of hydrodynamic diameter and Zeta potential of −23 mV. The antibacterial activity of ND-mTHPP was evaluated against Escherichia coli for different incubation times (0–24 h). The optimal activity was observed after 2 h of incubation and irradiation (660 nm; 51 J/cm2) performed right after the addition of ND-mTHPP (100 μg/mL) to the bacterial suspension. The inhibitory activity was 56% whereas ampicillin at the same conditions provided only 14% of bacterial growth inhibition. SEM images showed agglomerate of ND-mTHPP adsorbed on the bacterial cell wall, suggesting that the antimicrobial activity of ND-mTHPP was afforded by inducing membrane damage. Cytotoxicity against murine embryonic fibroblast cells (MEF) was also evaluated and ND-mTHPP was shown to be noncytotoxic since viability of cells cultured for 24 h in the presence of the nanoconjugate (100 μg/mL) was 78%. Considering the enhanced antibacterial activity and the absence of cytotoxic effect, it is possible to consider the ND-mTHPP nanoconjugate as promising platform for application in antimicrobial photodynamic therapy (aPDT). Full article
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