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12 pages, 3478 KiB

Open AccessArticle

Characterization of Increased Extracellular Vesicle-Mediated Tigecycline Resistance in Acinetobacter baumannii

by Hyejin Cho, Tesalonika Sondak and Kwang-sun Kim

Pharmaceutics 2023, 15(4), 1251; https://doi.org/10.3390/pharmaceutics15041251 - 15 Apr 2023

Cited by 7 | Viewed by 2455

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is the most detrimental pathogen that causes hospital-acquired infections. Tigecycline (TIG) is currently used as a potent antibiotic for treating CRAB infections; however, its overuse substantially induces the development of resistant isolates. Some molecular aspects of the resistance mechanisms [...] Read more.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is the most detrimental pathogen that causes hospital-acquired infections. Tigecycline (TIG) is currently used as a potent antibiotic for treating CRAB infections; however, its overuse substantially induces the development of resistant isolates. Some molecular aspects of the resistance mechanisms of AB to TIG have been reported, but they are expected to be far more complicated and diverse than what has been characterized thus far. In this study, we identified bacterial extracellular vesicles (EVs), which are nano-sized lipid-bilayered spherical structures, as mediators of TIG resistance. Using laboratory-made TIG-resistant AB (TIG-R AB), we demonstrated that TIG-R AB produced more EVs than control TIG-susceptible AB (TIG-S AB). Transfer analysis of TIG-R AB-derived EVs treated with proteinase or DNase to recipient TIG-S AB showed that TIG-R EV proteins are major factors in TIG resistance transfer. Additional transfer spectrum analysis demonstrated that EV-mediated TIG resistance was selectively transferred to Escherichia coli, Salmonella typhimurium, and Proteus mirabilis. However, this action was not observed in Klebsiella pneumonia and Staphylococcus aureus. Finally, we showed that EVs are more likely to induce TIG resistance than antibiotics. Our data provide direct evidence that EVs are potent cell-derived components with a high, selective occurrence of TIG resistance in neighboring bacterial cells. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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12 pages, 285 KiB

Open AccessArticle

Real-World Safety Profile of Biologics Used in Rheumatology: A Six-Year Observational Pharmacovigilance Study in the Calabria Region

by Agnese Gagliardi, Francesco Salvatore Iaquinta, Rosa Daniela Grembiale, Caterina De Sarro, Antonio Fabiano, Domenico Fraija, Caterina Palleria, Rossella Romeo, Adele Emanuela De Francesco, Maria Diana Naturale, Rita Citraro, Luca Gallelli, Antonio Leo and Giovambattista De Sarro

Pharmaceutics 2022, 14(11), 2328; https://doi.org/10.3390/pharmaceutics14112328 - 28 Oct 2022

Cited by 5 | Viewed by 1628

Abstract

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. [...] Read more.

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. This pharmacovigilance project aimed to study the AEs associated with biologics use in rheumatology. Methods: The current investigation is a multicenter, prospective, observational cohort study based on the Calabria Biologics Pharmacovigilance Program. Patients treated with one biologic agent from January 2016 to January 2022 were enrolled. Results: Overall, 729 (86.3%) of a total of 872 patients did not develop AEs or SAEs, whereas 143 (16.4%) patients experienced at least one AE, of which 16 (1.8%) had at least one SAE. The most common AEs were administration site conditions followed by gastrointestinal, nervous system and skin disorders. We reported a total of 173 switches and 156 swaps. Switches mainly occurred for inefficacy (136; 77.7%), whereas only 39 (22.3%) were due to the onset of an AE. Primary/secondary failure was the most frequent reason for swaps (124, 79%), while AEs onset led to 33 (21%) swaps. Conclusions: This study supports the validity of our program in monitoring and detecting AEs in the rheumatological area, confirming the positive beneficial/risk ratio of biologics. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

10 pages, 5714 KiB

Open AccessArticle

Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy

by Daniel Sandín, Javier Valle, Jordi Morata, David Andreu and Marc Torrent

Pharmaceutics 2022, 14(10), 2169; https://doi.org/10.3390/pharmaceutics14102169 - 11 Oct 2022

Cited by 3 | Viewed by 2017

Abstract

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate [...] Read more.

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-á-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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18 pages, 3118 KiB

Open AccessArticle

Innovative Insights into In Vitro Activity of Colloidal Platinum Nanoparticles against ESBL-Producing Strains of Escherichia coli and Klebsiella pneumoniae

by Damir Vukoja, Josipa Vlainić, Vanja Ljolić Bilić, Lela Martinaga, Iva Rezić, Diana Brlek Gorski and Ivan Kosalec

Pharmaceutics 2022, 14(8), 1714; https://doi.org/10.3390/pharmaceutics14081714 - 17 Aug 2022

Cited by 10 | Viewed by 2069

Abstract

Growing morbidity and mortality rates due to increase in the number of infections caused by MDR (multi-drug resistant) microorganisms are becoming some of the foremost global health issues. Thus, the need to search for and find novel approaches to fight AMR (antimicrobial resistance) [...] Read more.

Growing morbidity and mortality rates due to increase in the number of infections caused by MDR (multi-drug resistant) microorganisms are becoming some of the foremost global health issues. Thus, the need to search for and find novel approaches to fight AMR (antimicrobial resistance) has become obligatory. This study aimed to determine the antimicrobial properties of commercially purchased colloidal platinum nanoparticles by examining the existence and potency of their antibacterial effects and investigating the mechanisms by means of which they express these activities. Antimicrobial properties were investigated with respect to standard laboratory ATCC (American Type Cell Culture) and clinical extended-spectrum beta-lactamase (ESBL)-producing strains of Escherichia (E.) coli and Klebsiella (K.) pneumoniae. Standard microbiological methods of serial microdilution, modulation of microbial cell death kinetics (“time–kill” assays), and biofilm inhibition were used. Bacterial cell wall damage and ROS (reactive oxygen species) levels were assessed in order to explore the mechanisms of platinum nanoparticles’ antibacterial activities. Platinum nanoparticles showed strong antibacterial effects against all tested bacterial strains, though their antibacterial effects were found to succumb to time kinetics. Antibiofilm activity was modest overall and significantly effective only against E. coli strains. By measuring extracellular DNA/RNA and protein concentrations, induced bacterial cell wall damage could be assumed. The determination of ROS levels induced by platinum nanoparticles revealed their possible implication in antibacterial activity. We conclude that platinum nanoparticles exhibit potent antibacterial effects against standard laboratory and resistant strains of E. coli and K. pneumoniae. Both, cell wall damage and ROS induction could have important role as mechanisms of antibacterial activity, and, require further investigation. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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12 pages, 3746 KiB

Open AccessArticle

Exploring the Diverse Morphology of Porous Poly(Lactic Acid) Fibers for Developing Long-Term Controlled Antibiotic Delivery Systems

by Kwon Ho Seo, Kyung Eun Lee, Meltem Yanilmaz and Juran Kim

Pharmaceutics 2022, 14(6), 1272; https://doi.org/10.3390/pharmaceutics14061272 - 15 Jun 2022

Cited by 7 | Viewed by 1836

Abstract

In this study, we aimed to explore the morphologies of porous poly(lactic acid) (PLA) fibers through liquid–liquid phase separation, and investigate the relationship among pore formation, physical properties, and antibacterial activities of the fibers for identifying their potential as drug delivery carriers. Antibacterial [...] Read more.

In this study, we aimed to explore the morphologies of porous poly(lactic acid) (PLA) fibers through liquid–liquid phase separation, and investigate the relationship among pore formation, physical properties, and antibacterial activities of the fibers for identifying their potential as drug delivery carriers. Antibacterial activities of gentamicin-, kanamycin-, and amikacin-loaded PLA fibers against E. coli and S. epidermidis were evaluated. The antibacterial activity of drugs against E. coli showed the following profile: gentamicin > amikacin > kanamycin; however, S. epidermidis growth was almost completely inhibited immediately after the administration of all three drugs. The efficiency of gentamicin can be attributed to the electrostatic interactions between the positively and negatively charged antibiotic and bacterial cell membrane, respectively. Furthermore, gentamicin-loaded porous PLA fibers were evaluated as drug delivery systems. The cumulative amount of gentamicin in porous PLA nanofibers was considerably higher than that in other PLA fibers for 168 h, followed by 7:3 PLA > 6:4 PLA > 5:5 PLA > non-porous PLA. The 7:3 PLA fibers were projected to be ideal drug carrier candidates for controlled antibiotic release in delivery systems owing to their interconnected internal structure and the largest surface area (55.61 m² g⁻¹), pore size (42.19 nm), and pore volume (12.78 cm³ g⁻¹). Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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14 pages, 3773 KiB

Open AccessArticle

Integrating In Vitro and In Silico Analysis of a Cationic Antimicrobial Peptide Interaction with Model Membranes of Colistin-Resistant Pseudomonas aeruginosa Strains

by Sandra Patricia Rivera-Sanchez, Iván Darío Ocampo-Ibáñez, Yamil Liscano, Natalia Martínez, Isamar Muñoz, Marcela Manrique-Moreno, Luis Martinez-Martinez and José Oñate-Garzon

Pharmaceutics 2022, 14(6), 1248; https://doi.org/10.3390/pharmaceutics14061248 - 12 Jun 2022

Cited by 9 | Viewed by 2636

Abstract

Bacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. [...] Read more.

Bacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. Accordingly, cationic antimicrobial peptides (CAMPs) have emerged as promising alternatives to control resistant bacteria. In this study, the interaction of a CAMP derived from cecropin D-like (∆M2) with model membranes mimicking bacterial biomembranes of wild-type (WTPa) strains of P. aeruginosa and CRPa was evaluated through in vitro and in silico approaches. In vitro interaction was determined by infrared spectroscopy, whereas in silico molecular dynamics was performed to predict specific interactions between amino acids of ∆M2 and lipids of model membrane systems. Experimental analysis showed this peptide interacted with the lipids of bacterial-like model membranes of WTPa and CRPa. In both cases, an increase in the concentration of peptides induced an increase in the phase transition temperature of the lipid systems. On the other hand, the peptides in solution underwent a transition from a random to a helical secondary structure after interacting with the membranes mostly favored in the CRPa system. The α-helix structure percentage for ΔM2 interacting with WTPa and CRPa lipid systems was 6.4 and 33.2%, respectively. Finally, molecular dynamics showed ∆M2 to have the most affinities toward the phospholipids palmitoyl-oleyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) that mimic membranes of WTPa and CRPa, respectively. This work provides clues for elucidating the membrane-associated mechanism of action of ∆M2 against colistin-susceptible and -resistant strains of Pseudomonas aeruginosa. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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15 pages, 3512 KiB

Open AccessArticle

Co-Loading of Inorganic Nanoparticles and Natural Oil in the Electrospun Janus Nanofibers for a Synergetic Antibacterial Effect

by Menglong Wang, Deng-Guang Yu, Gareth R. Williams and Sim Wan Annie Bligh

Pharmaceutics 2022, 14(6), 1208; https://doi.org/10.3390/pharmaceutics14061208 - 6 Jun 2022

Cited by 48 | Viewed by 3930

Abstract

Side-by-side electrospinning is a powerful but challenging technology that can be used to prepare Janus nanofibers for various applications. In this work, cellulose acetate (CA) and polycaprolactone (PCL) were used as polymer carriers for silver nanoparticles (Ag NPs) and lavender oil (LO), respectively, [...] Read more.

Side-by-side electrospinning is a powerful but challenging technology that can be used to prepare Janus nanofibers for various applications. In this work, cellulose acetate (CA) and polycaprolactone (PCL) were used as polymer carriers for silver nanoparticles (Ag NPs) and lavender oil (LO), respectively, processing these into two-compartment Janus fibers. A bespoke spinneret was used to facilitate the process and prevent the separation of the working fluids. The process of side-by-side electrospinning was recorded with a digital camera, and the morphology and internal structure of the products were characterized by electron microscopy. Clear two-compartment fibers are seen. X-ray diffraction patterns demonstrate silver nanoparticles have been successfully loaded on the CA side, and infrared spectroscopy indicates LO is dispersed on the PCL side. Wetting ability and antibacterial properties of the fibers suggested that PCL-LO//CA-Ag NPs formulation had strong antibacterial activity, performing better than fibers containing only one active component. The PCL-LO//CA-Ag NPs had a 20.08 ± 0.63 mm inhibition zone for E. coli and 19.75 ± 0.96 mm for S. aureus. All the fibers had water contact angels all around 120°, and hence, have suitable hydrophobicity to prevent water ingress into a wound site. Overall, the materials prepared in this work have considerable promise for wound healing applications. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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20 pages, 13838 KiB

Open AccessEditor’s ChoiceArticle

Dextran-Coated Iron Oxide Nanoparticles Loaded with Curcumin for Antimicrobial Therapies

by Cristina Chircov, Raluca-Elena Ștefan, Georgiana Dolete, Adriana Andrei, Alina Maria Holban, Ovidiu-Cristian Oprea, Bogdan Stefan Vasile, Ionela Andreea Neacșu and Bianca Tihăuan

Pharmaceutics 2022, 14(5), 1057; https://doi.org/10.3390/pharmaceutics14051057 - 14 May 2022

Cited by 27 | Viewed by 3913

Abstract

The current trend in antimicrobial-agent development focuses on the use of natural compounds that limit the toxicity of conventional drugs and provide a potential solution to the antimicrobial resistance crisis. Curcumin represents a natural bioactive compound with well-known antimicrobial, anticancer, and antioxidant properties. [...] Read more.

The current trend in antimicrobial-agent development focuses on the use of natural compounds that limit the toxicity of conventional drugs and provide a potential solution to the antimicrobial resistance crisis. Curcumin represents a natural bioactive compound with well-known antimicrobial, anticancer, and antioxidant properties. However, its hydrophobicity considerably limits the possibility of body administration. Therefore, dextran-coated iron oxide nanoparticles can be used as efficient drug-delivery supports that could overcome this limitation. The iron oxide nanoparticles were synthesized through the microwave-assisted hydrothermal method by varying the treatment parameters (pressure and reaction time). The nanoparticles were subsequently coated with dextran and used for the loading of curcumin (in various concentrations). The drug-delivery systems were characterized through X-ray diffraction (XRD) coupled with Rietveld refinement, transmission electron microscopy (TEM), high-resolution TEM (HR-TEM), selected area electron diffraction (SAED), dynamic light scattering (DLS) and zeta potential, thermogravimetry and differential scanning calorimetry (TG-DSC), vibrating sample magnetometry (VSM), and UV-Vis spectrophotometry, as well as regarding their antimicrobial efficiency and biocompatibility using the appropriate assays. The results demonstrate a promising antimicrobial efficiency, as well as an increased possibility of controlling the properties of the resulted nanosystems. Thus, the present study represents an important step forward toward the development of highly efficient antimicrobial drug-delivery systems. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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15 pages, 2144 KiB

Open AccessArticle

Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria

by Hyejin Cho and Kwang-sun Kim

Pharmaceutics 2022, 14(3), 552; https://doi.org/10.3390/pharmaceutics14030552 - 1 Mar 2022

Cited by 1 | Viewed by 3214

Abstract

Multidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral antiviral agent, is a leading [...] Read more.

Multidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral antiviral agent, is a leading repurposed drug against MDR Gram-negative bacterial infections. However, the rapid emergence of bacterial resistance due to long-term exposure, overuse, or misuse limits its application, making it necessary to develop new alternatives. In this study, we investigated the efficacy of ciclopirox (CPX) as an alternative to AZT. The minimum inhibitory concentrations of AZT and CPX against MDR Gram-negative bacteria were determined; CPX appeared more active against β-lactamase-producing Escherichia coli, whereas AZT displayed no selectivity for any antibiotic-resistant strain. Motility assays revealed that β-lactamase-producing Escherichia coli strains were less motile in nature and more strongly affected by CPX than a parental strain. Resistance against CPX was not observed in E. coli even after 25 days of growth, whereas AZT resistance was observed in less than 2 days. Moreover, CPX effectively killed AZT-resistant strains with different resistance mechanisms. Our findings indicate that CPX may be utilized as an alternative or supplement to AZT-based medications to treat opportunistic Gram-negative bacterial infections. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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19 pages, 3755 KiB

Open AccessArticle

Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor

by Menka Drost, Eleonora Diamanti, Kathrin Fuhrmann, Adriely Goes, Atanaz Shams, Jörg Haupenthal, Marcus Koch, Anna K. H. Hirsch and Gregor Fuhrmann

Pharmaceutics 2022, 14(1), 4; https://doi.org/10.3390/pharmaceutics14010004 - 21 Dec 2021

Cited by 11 | Viewed by 4237

Abstract

Liposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading [...] Read more.

Liposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading method of bacteriomimetic liposomes for a novel, hydrophobic compound (HIPS5031) inhibiting energy-coupling factor transporters (ECF transporters), an underexplored antimicrobial target. The liposomes were composed of DOPG (18:1 (Δ9-cis) phosphatidylglycerol) and CL (cardiolipin), resembling the cell membrane of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and enriched with cholesterol (Chol). The size and polydispersity of the DOPG/CL/± Chol liposomes remained stable over 8 weeks when stored at 4 °C. Loading of the ECF transporter inhibitor was achieved by thin film hydration and led to a high encapsulation efficiency of 33.19% ± 9.5% into the DOPG/CL/Chol liposomes compared to the phosphatidylcholine liposomes (DMPC/DPPC). Bacterial growth inhibition assays on the model organism Bacillus subtilis revealed liposomal HIPS5031 as superior to the free drug, showing a 3.5-fold reduction in CFU/mL at a concentration of 9.64 µM. Liposomal HIPS5031 was also shown to reduce B. subtilis biofilm. Our findings present an explorative basis for bacteriomimetic liposomes as a strategy against drug-resistant pathogens by surpassing the drug-formulation barriers of innovative, yet unfavorably hydrophobic, antibiotics. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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24 pages, 6829 KiB

Open AccessArticle

Biogenic ZnO Nanoparticles Synthesized from Origanum vulgare Abrogates Quorum Sensing and Biofilm Formation in Opportunistic Pathogen Chromobacterium violaceum

by Majid Rasool Kamli, Maqsood Ahmad Malik, Vartika Srivastava, Jamal S. M. Sabir, Ehab H. Mattar and Aijaz Ahmad

Pharmaceutics 2021, 13(11), 1743; https://doi.org/10.3390/pharmaceutics13111743 - 20 Oct 2021

Cited by 15 | Viewed by 2974

Abstract

This study presents an inexpensive, eco-friendly, and simple green synthesis of ZnO nanoparticles using Origanum vulgare extract. These nanoparticles are non-hazardous, environmentally friendly, and cheaper than other methods of biosynthesis. Ongoing research determines the role of phytochemicals in the fabrication and biosynthesis of [...] Read more.

This study presents an inexpensive, eco-friendly, and simple green synthesis of ZnO nanoparticles using Origanum vulgare extract. These nanoparticles are non-hazardous, environmentally friendly, and cheaper than other methods of biosynthesis. Ongoing research determines the role of phytochemicals in the fabrication and biosynthesis of ZnO NPs and their role in antibacterial activity and biomedical applications. Characterizations by fourier transform infrared spectroscopy (FTIR), diffuse reflectance UV-visible spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) determine the successful biosynthesis of ZnO NPs. Meanwhile, TEM and X-ray diffraction studies approximated the spherical morphology and crystalline nature of biosynthesized ZnO NPs of nano size in the range of 20–30 nm. The global increase in drug resistance necessitates the search for new drugs with different mechanisms of action. Quorum sensing (QS), a cell-to-cell communication, has gained attention as an emerging drug target. It controls numerous biochemical processes in bacteria, which are essential for their survival and pathogenicity. The potential of nanomedicines has also been tested to synthesize new antibiotics to tackle drug resistance. ZnO NPs were explored for their antibacterial, antiquorum sensing, and antibiofilm activities with a bioreporter strain of Chromobacterium violaceum. Susceptibility testing results indicated the potential antibacterial activity of ZnO NPs with a minimum inhibitory concentration (MIC) of 4 µg/mL and minimum bactericidal concentration (MBC) of 16 µg/mL. Antiquorum-sensing assays revealed that these nanoparticles inhibit quorum sensing with minimum antiquorum sensing activity (MQSIC) of 1 µg/mL, without causing any bacterial growth inhibition. In addition, ZnO NPs inhibit biofilm formation at inhibitory and higher concentrations. RT-qPCR results supported the downregulation of the quorum sensing genes when C. violaceum was treated with ZnO NPs. The outcomes of this study are promising with regard to the biofilm and quorum sensing, emphasizing the potential applications of ZnO NPs against bacterial communication and biofilm formation. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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16 pages, 2065 KiB

Open AccessArticle

Multicomponent Peptide Hydrogels as an Innovative Platform for Cell-Based Tissue Engineering in the Dental Pulp

by Marina E. Afami, Ikhlas El Karim, Imad About, Anna D. Krasnodembskaya, Garry Laverty and Fionnuala T. Lundy

Pharmaceutics 2021, 13(10), 1575; https://doi.org/10.3390/pharmaceutics13101575 - 28 Sep 2021

Cited by 18 | Viewed by 2654

Abstract

In light of the increasing levels of antibiotic resistance, nanomaterials and novel biologics are urgently required to manage bacterial infections. To date, commercially available self-assembling peptide hydrogels have not been studied extensively for their ability to inhibit micro-organisms relevant to tissue engineering sites [...] Read more.

In light of the increasing levels of antibiotic resistance, nanomaterials and novel biologics are urgently required to manage bacterial infections. To date, commercially available self-assembling peptide hydrogels have not been studied extensively for their ability to inhibit micro-organisms relevant to tissue engineering sites such as dental root canals. In this work, we assess the biocompatibility of dental pulp stem/stromal cells with commercially available multicomponent peptide hydrogels. We also determine the effects of dental pulp stem/stromal cell (DPSC) culture in hydrogels on growth factor/cytokine expression. Furthermore, to investigate novel aspects of self-assembling peptide hydrogels, we determine their antimicrobial activity against the oral pathogens Staphylococcus aureus, Enterococcus faecalis, and Fusobacterium nucleatum. We show that self-assembling peptide hydrogels and hydrogels functionalized with the adhesion motif Arg-Gly-Asp (RGD) are biocompatible with DPSCs, and that cells grown in 3D hydrogel cultures produce a discrete secretome compared with 2D-cultured cells. Furthermore, we show that soluble peptides and assembled hydrogels have antimicrobial effects against oral pathogens. Given their antibacterial activity against oral pathogens, biocompatibility with dental pulp stem/stromal cells and enhancement of an angiogenic secretome, multicomponent peptide hydrogels hold promise for translational use. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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14 pages, 1968 KiB

Open AccessArticle

Lipoplexes to Deliver Oligonucleotides in Gram-Positive and Gram-Negative Bacteria: Towards Treatment of Blood Infections

by Sara Pereira, Rita Sobral Santos, Luís Moreira, Nuno Guimarães, Mariana Gomes, Heyang Zhang, Katrien Remaut, Kevin Braeckmans, Stefaan De Smedt and Nuno Filipe Azevedo

Pharmaceutics 2021, 13(7), 989; https://doi.org/10.3390/pharmaceutics13070989 - 29 Jun 2021

Cited by 10 | Viewed by 4893

Abstract

Bacterial resistance to antibiotics threatens the ability to treat life-threatening bloodstream infections. Oligonucleotides (ONs) composed of nucleic acid mimics (NAMs) able to inhibit essential genes can become an alternative to traditional antibiotics, as long as they are safely transported in human serum upon [...] Read more.

Bacterial resistance to antibiotics threatens the ability to treat life-threatening bloodstream infections. Oligonucleotides (ONs) composed of nucleic acid mimics (NAMs) able to inhibit essential genes can become an alternative to traditional antibiotics, as long as they are safely transported in human serum upon intravenous administration and they are carried across the multilayered bacterial envelopes, impermeable to ONs. In this study, fusogenic liposomes were considered to transport the ONs and promote their internalization in clinically relevant bacteria. Locked nucleic acids and 2′-OMethyl RNA were evaluated as model NAMs and formulated into DOTAP–DOPE liposomes followed by post-PEGylation. Our data showed a complexation stability between the post-PEGylated liposomes and the ONs of over 82%, during 24 h in native human serum, as determined by fluorescence correlation spectroscopy. Quantification by a lipid-mixing assay showed that liposomes, with and without post-PEGylation, fused with all bacteria tested. Such fusion promoted the delivery of a fraction of the ONs into the bacterial cytosol, as observed by fluorescence in situ hybridization and bacterial fractionation. In short, we demonstrated for the first time that liposomes can safely transport ONs in human serum and intracellularly deliver them in both Gram-negative and -positive bacteria, which holds promise towards the treatment of bloodstream infections. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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Review

Jump to: Research

25 pages, 2589 KiB

Open AccessReview

Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems

by Mohammad Imran, Saurav Kumar Jha, Nazeer Hasan, Areeba Insaf, Jitendra Shrestha, Jesus Shrestha, Hari Prasad Devkota, Salman Khan, Nisha Panth, Majid Ebrahimi Warkiani, Kamal Dua, Philip M. Hansbro, Keshav Raj Paudel and Yousuf Mohammed

Pharmaceutics 2022, 14(3), 586; https://doi.org/10.3390/pharmaceutics14030586 - 8 Mar 2022

Cited by 29 | Viewed by 8530

Abstract

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug [...] Read more.

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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28 pages, 5340 KiB

Open AccessReview

Advances in the Application of Nanomaterials as Treatments for Bacterial Infectious Diseases

by Yuan-Pin Hung, Yu-Fon Chen, Pei-Jane Tsai, I-Hsiu Huang, Wen-Chien Ko and Jeng-Shiung Jan

Pharmaceutics 2021, 13(11), 1913; https://doi.org/10.3390/pharmaceutics13111913 - 12 Nov 2021

Cited by 11 | Viewed by 3971

Abstract

Bacteria-targeting nanomaterials have been widely used in the diagnosis and treatment of bacterial infectious diseases. These nanomaterials show great potential as antimicrobial agents due to their broad-spectrum antibacterial capacity and relatively low toxicity. Recently, nanomaterials have improved the accurate detection of pathogens, provided [...] Read more.

Bacteria-targeting nanomaterials have been widely used in the diagnosis and treatment of bacterial infectious diseases. These nanomaterials show great potential as antimicrobial agents due to their broad-spectrum antibacterial capacity and relatively low toxicity. Recently, nanomaterials have improved the accurate detection of pathogens, provided therapeutic strategies against nosocomial infections and facilitated the delivery of antigenic protein vaccines that induce humoral and cellular immunity. Biomaterial implants, which have traditionally been hindered by bacterial colonization, benefit from their ability to prevent bacteria from forming biofilms and spreading into adjacent tissues. Wound repair is improving in terms of both the function and prevention of bacterial infection, as we tailor nanomaterials to their needs, select encapsulation methods and materials, incorporate activation systems and add immune-activating adjuvants. Recent years have produced numerous advances in their antibacterial applications, but even further expansion in the diagnosis and treatment of infectious diseases is expected in the future. Full article

(This article belongs to the Special Issue Nanomaterials and Novel Biologics to Manage Bacterial Infections)

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