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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 August 2022) | Viewed by 33475

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Prof. Dr. Fu-Gen Wu

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State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, China
Interests: biosensors; drug delivery; nanomedicine; cancer therapy; antibacterial; pharmaceuticals
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Dear Colleagues,

Microbial infections have always posed a threat to public health, and the situation is becoming worse as some strains of these microorganisms develop drug resistance to drugs such as conventional antibiotics. With the rapid development of nanotechnology and nanomaterials, an increasing number of nanodrugs capable of fighting against various microorganisms (e.g., bacteria, fungi, and viruses) have been designed and prepared. The diversified size, shape, and chemical characteristics enable nanomaterials to facilitate molecular interactions with the microorganisms, and the high surface to volume ratio allows incorporation of abundant functional moieties to these nanomaterials, thus promoting multivalent interactions with the microorganism. To date, the most commonly used antimicrobial nanomaterials include conventional metal (Ag, Cu, Zn, and Ti)-containing nanoagents, two-dimensional nanoagents (e.g., graphene materials, layered double hydroxides, transition-metal dichalcogenides, graphitic carbon nitride, MXenes, black phosphorus, and their derivatives), polymeric nanomaterials, nanomicelles and nanovesicles, carbon dots and silicon nanoparticles, aggregation-induced emission (AIE) nanodots, nanocomposite materials, etc. In addition, the nanomaterials with specific light-, heat-, electricity-, magnetic field-, and ultrasound-responsive properties, as well as excellent antimicrobial activity, have also attracted the interest from a growing number of researchers. Common examples include nanoagents with photodynamic therapy capacity and sonodynamic therapy activity. Further, nanozymes with antimicrobial activity have also drawn tremendous research interest from many researchers worldwide. In addition, chemodynamic therapy that utilizes Fenton or Fenton-like reactions to kill microbial cells represents an emerging research direction. Finally, the nanomaterials decorated with conventional antibiotics have also shown the potential for achieving enhanced antimicrobial capacity compared to free antibiotics.

The journal Pharmaceuticals invites both original articles and reviews regarding the use of nanomaterials and nanodrugs for antimicrobial applications. The related topics include: metal-based nanodrugs for antimicrobial applications, metal-free nanodrugs for antimicrobial applications, and hybrid nanodrugs for antimicrobial applications. We also welcome papers that investigate the interaction mechanisms between nanomaterials/nanodrugs and microorganisms (bacteria, fungi, and viruses). The collection of manuscripts will be published as a Special Issue of the journal.

Prof. Dr. Fu-Gen Wu
Guest Editor

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Keywords

nanomaterials
nanoagents
bacteria
antibacterial
antimicrobial
biofilms
drug-resistance
antibiotics
phototherapy
nanozymes

Published Papers (10 papers)

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Research

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18 pages, 3366 KiB

Open AccessArticle

Novel In Vivo Assessment of Antimicrobial Efficacy of Ciprofloxacin Loaded Mesoporous Silica Nanoparticles against Salmonella typhimurium Infection

by Maher N. Alandiyjany, Ahmed S. Abdelaziz, Ahmed Abdelfattah-Hassan, Wael A. H. Hegazy, Arwa A. Hassan, Sara T. Elazab, Eman A. A. Mohamed, Eman S. El-Shetry, Ayman A. Saleh, Naser A. ElSawy and Doaa Ibrahim

Pharmaceuticals 2022, 15(3), 357; https://doi.org/10.3390/ph15030357 - 15 Mar 2022

Cited by 35 | Viewed by 3540

Abstract

Salmonella enterica serovar Typhimurium (S. typhimurium) is known for its intracellular survival, evading the robust inflammation and adaptive immune response of the host. The emergence of decreased ciprofloxacin (CIP) susceptibility (DCS) requires a prolonged antibiotic course with increased dosage, leading to threatening, adverse effects. Moreover, antibiotic-resistant bacteria can persist in biofilms, causing serious diseases. Hence, we validated the in vitro and in vivo efficacy of ciprofloxacin-loaded mesoporous silica nanoparticles (CIP–MSN) using a rat model of salmonella infection to compare the oral efficacy of 5 mg/kg body weight CIP–MSN and a traditional treatment regimen with 10 mg/kg CIP postinfection. Our results revealed that mesoporous silica particles can regulate the release rate of CIP with an MIC of 0.03125 mg/L against DCS S. typhimurium with a greater than 50% reduction of biofilm formation without significantly affecting the viable cells residing within the biofilm, and a sub-inhibitory concentration of CIP–MSN significantly reduced invA and FimA gene expressions. Furthermore, oral supplementation of CIP–MSN had an insignificant effect on all blood parameter values as well as on liver and kidney function parameters. MPO and NO activities that are key mediators of oxidative stress were abolished by CIP–MSN supplementation. Additionally, CIP–MSN supplementation has a promising role in attenuating the elevated secretion of pro-inflammatory cytokines and chemokines in serum from S. typhimurium-infected rats with a reduction in pro-apoptotic gene expression, resulting in reduced S. typhimurium-induced hepatic apoptosis. This counteracted the negative effects of the S. typhimurium challenge, as seen in a corrected histopathological picture of both the intestine and liver, along with increased bacterial clearance. We concluded that, compared with a normal ciprofloxacin treatment regime, MSN particles loaded with a half-dose of ciprofloxacin exhibited controlled release of the antibiotic, which can prolong the antibacterial effect. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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11 pages, 5004 KiB

Open AccessArticle

Azeotropic Distillation-Induced Self-Assembly of Mesostructured Spherical Nanoparticles as Drug Cargos for Controlled Release of Curcumin

by Long Chen, Xin Fu, Mei Lin and Xingmao Jiang

Pharmaceuticals 2022, 15(3), 275; https://doi.org/10.3390/ph15030275 - 23 Feb 2022

Cited by 1 | Viewed by 1631

Abstract

Methods of large-scale controllable production of uniform monodispersed spherical nanoparticles have been one of the research directions of scientists in recent years. In this paper, we report an azeotropic distillation-induced evaporation self-assembly method as a universal method, and monodispersed hydrophobic ordered mesoporous silica nanospheres (MHSs) were successfully synthesized by this method, using triethoxymethylsilane (MTES) as the silica precursor and hexadecyl trimethyl ammonium bromide (CTAB) as the template. SEM and TEM images showed good monodispersity, sphericity, and uniform diameter. Meanwhile, SAXS and N₂ adsorption–desorption measurements demonstrated a highly ordered lamellar mesostructure with a large pore volume. The model drug, curcumin was successfully encapsulated in MHSs for drug delivery testing, and their adsorption capacity was 3.45 mg g⁻¹, which greatly improved the stability of curcumin. The release time when net release rate of curcumin reached 50% was extended to 6 days. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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22 pages, 7850 KiB

Open AccessArticle

In Vivo and In Vitro Antimicrobial Activity of Biogenic Silver Nanoparticles against Staphylococcus aureus Clinical Isolates

by Nashwah G. M. Attallah, Engy Elekhnawy, Walaa A. Negm, Ismail A. Hussein, Fatma Alzahraa Mokhtar and Omnia Momtaz Al-Fakhrany

Pharmaceuticals 2022, 15(2), 194; https://doi.org/10.3390/ph15020194 - 03 Feb 2022

Cited by 43 | Viewed by 3901

Abstract

Staphylococcus aureus can cause a wide range of severe infections owing to its multiple virulence factors in addition to its resistance to multiple antimicrobials; therefore, novel antimicrobials are needed. Herein, we used Gardenia thailandica leaf extract (GTLE), for the first time for the biogenic synthesis of silver nanoparticles (AgNPs). The active constituents of GTLE were identified by HPLC, including chlorogenic acid (1441.03 μg/g) from phenolic acids, and quercetin-3-rutinoside (2477.37 μg/g) and apigenin-7-glucoside (605.60 μg/g) from flavonoids. In addition, the antioxidant activity of GTLE was evaluated. The synthesized AgNPs were characterized using ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, transmission and scanning electron microscopy (SEM), zeta potential, dynamic light scattering, and X-ray diffraction. The formed AgNPs had a spherical shape with a particle size range of 11.02–17.92 nm. The antimicrobial activity of AgNPs was investigated in vitro and in vivo against S. aureus clinical isolates. The minimum inhibitory concentration (MIC) of AgNPs ranged from 4 to 64 µg/mL. AgNPs significantly decreased the membrane integrity of 45.8% of the isolates and reduced the membrane potential by flow cytometry. AgNPs resulted in morphological changes observed by SEM. Furthermore, qRT-PCR was utilized to examine the effect of AgNPs on the gene expression of the efflux pump genes norA, norB, and norC. The in vivo examination was performed on wounds infected with S. aureus bacteria in rats. AgNPs resulted in epidermis regeneration and reduction in the infiltration of inflammatory cells. Thus, GTLE could be a vital source for the production of AgNPs, which exhibited promising in vivo and in vitro antibacterial activity against S. aureus bacteria. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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12 pages, 3721 KiB

Open AccessEditor’s ChoiceArticle

Sensitization of Antibiotic-Resistant Gram-Negative Bacteria to Photodynamic Therapy via Perfluorocarbon Nanoemulsion

by Peiyuan Niu, Jialing Dai, Zeyu Wang, Yueying Wang, Duxiang Feng, Yuanyuan Li and Wenjun Miao

Pharmaceuticals 2022, 15(2), 156; https://doi.org/10.3390/ph15020156 - 27 Jan 2022

Cited by 9 | Viewed by 3883

Abstract

With the merits of excellent efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents a promising means for treating bacterial infections. However, APDT shows an unsatisfactory efficacy in combating antibiotic-resistant Gram-negative bacteria due to their specific cell wall structure. In this work, we report a perfluorocarbon nanoemulsion (Ce6@FDC) used as a multifunctional nanocargo of photosensitizer and oxygen for sensitizing antibiotic-resistant Gram-negative bacteria to APDT. Ce6@FDC was fabricated via ultrasonic emulsification with good colloidal stability, efficient Ce6 and oxygen delivery, and excellent photodynamic activity. Meanwhile, Ce6@FDC could strongly bind with Gram-negative Acinetobacter baumannii (A. baumannii) and Escherichia coli (E. coli) via electrostatic interaction, thus leading to notable photodynamic bactericidal potency upon irradiation. In addition, oxygenated Ce6@FDC also exhibited a remarkable efficacy in eradicating Gram-negative bacteria biofilm, averaging five log units lower than the Ce6 group under identical conditions. Taken together, we demonstrate that photodynamic perfluorocarbon nanoemulsion with oxygen-delivery ability could effectively kill planktonic bacteria and remove biofilm, representing a novel strategy in fighting against antibiotic-resistant Gram-negative bacteria. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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21 pages, 920 KiB

Open AccessArticle

In Vitro Antibacterial Susceptibility of Different Pathogens to Thirty Nano-Polyoxometalates

by Ștefana Bâlici, Dan Rusu, Emőke Páll, Miuța Filip, Flore Chirilă, Gheorghe Zsolt Nicula, Mihaela Laura Vică, Rodica Ungur, Horea Vladi Matei and Nicodim Iosif Fiț

Pharmaceuticals 2022, 15(1), 33; https://doi.org/10.3390/ph15010033 - 27 Dec 2021

Cited by 5 | Viewed by 2579

Abstract

Due to their unique properties, nano-polyoxometalates (POMs) can be alternative chemotherapeutic agents instrumental in designing new antibiotics. In this research, we synthesized and characterized “smart” nanocompounds and validated their antibacterial effects in order to formulate and implement potential new drugs. We characterized thirty POMs in terms of antibacterial activity–structure relationship. The antibacterial effects of these compounds are directly dependent upon their structure and the type of bacterial strain tested. We identified three POMs that presented sound antibacterial activity against S. aureus, B. cereus, E. coli, S. enteritidis and P. aeruginosa strains. A newly synthesized compound K₆[(VO)SiMo₂W₉O₃₉]·11H₂O (POM 7) presented antibacterial activity only against S. aureus (ATCC 6538P). Twelve POMs exerted antibacterial effects against both Gram-positive and Gram-negative strains. Only one POM (a cluster derivatized with organometallic fragments) exhibited a stronger effect compared to amoxicillin. New studies in terms of selectivity and specificity are required to clarify these extremely important aspects needed to be considered in drug design. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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9 pages, 5105 KiB

Open AccessArticle

Effect of Plasmonic Gold Nanoprisms on Biofilm Formation and Heat Shock Proteins Expression in Human Pathogenic Bacteria

by Rihab Lagha, Fethi Ben Abdallah, Amine Mezni and Othman M. Alzahrani

Pharmaceuticals 2021, 14(12), 1335; https://doi.org/10.3390/ph14121335 - 20 Dec 2021

Cited by 4 | Viewed by 2354

Abstract

Gold nanoparticles have gained interest in biomedical sciences in the areas of nano-diagnostics, bio-labeling, drug delivery, and bacterial infection. In this study, we examined, for the first time, the antibacterial and antibiofilm properties of plasmonic gold nanoprisms against human pathogenic bacteria using MIC and crystal violet. In addition, the expression level of GroEL/GroES heat shock proteins was also investigated by western blot. Gold nanoparticles were characterized by TEM and EDX, which showed equilateral triangular prisms with an average edge length of 150 nm. Antibacterial activity testing showed a great effect of AuNPs against pathogenic bacteria with MICs values ranging from 50 μg/mL to 100 μg/mL. Nanoparticles demonstrated strong biofilm inhibition action with a percentage of inhibition ranging from 40.44 to 82.43%. Western blot analysis revealed that GroEL was an AuNPs-inducible protein with an increase of up to 66.04%, but GroES was down-regulated with a reduction of up to 46.81%. Accordingly, plasmonic gold nanoprisms, could be a good candidate for antibiotics substitution in order to treat bacterial infections. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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Review

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34 pages, 6542 KiB

Open AccessReview

Targeted Anti-Biofilm Therapy: Dissecting Targets in the Biofilm Life Cycle

by Fanqiang Bu, Mengnan Liu, Zixu Xie, Xinyu Chen, Guofeng Li and Xing Wang

Pharmaceuticals 2022, 15(10), 1253; https://doi.org/10.3390/ph15101253 - 12 Oct 2022

Cited by 2 | Viewed by 3944

Abstract

Biofilm is a crucial virulence factor for microorganisms that causes chronic infection. After biofilm formation, the bacteria present improve drug tolerance and multifactorial defense mechanisms, which impose significant challenges for the use of antimicrobials. This indicates the urgent need for new targeted technologies and emerging therapeutic strategies. In this review, we focus on the current biofilm-targeting strategies and those under development, including targeting persistent cells, quorum quenching, and phage therapy. We emphasize biofilm-targeting technologies that are supported by blocking the biofilm life cycle, providing a theoretical basis for design of targeting technology that disrupts the biofilm and promotes practical application of antibacterial materials. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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20 pages, 4610 KiB

Open AccessReview

Carbon Dots for Killing Microorganisms: An Update since 2019

by Fengming Lin, Zihao Wang and Fu-Gen Wu

Pharmaceuticals 2022, 15(10), 1236; https://doi.org/10.3390/ph15101236 - 08 Oct 2022

Cited by 11 | Viewed by 3169

Abstract

Frequent bacterial/fungal infections and occurrence of antibiotic resistance pose increasing threats to the public and thus require the development of new antibacterial/antifungal agents and strategies. Carbon dots (CDs) have been well demonstrated to be promising and potent antimicrobial nanomaterials and serve as potential alternatives to conventional antibiotics. In recent years, great efforts have been made by many researchers to develop new carbon dot-based antimicrobial agents to combat microbial infections. Here, as an update to our previous relevant review (C 2019, 5, 33), we summarize the recent achievements in the utilization of CDs for microbial inactivation. We review four kinds of antimicrobial CDs including nitrogen-doped CDs, metal-containing CDs, antibiotic-conjugated CDs, and photoresponsive CDs in terms of their starting materials, synthetic route, surface functionalization, antimicrobial ability, and the related antimicrobial mechanism if available. In addition, we summarize the emerging applications of CD-related antimicrobial materials in medical and industry fields. Finally, we discuss the existing challenges of antimicrobial CDs and the future research directions that are worth exploring. We believe that this review provides a comprehensive overview of the recent advances in antimicrobial CDs and may inspire the development of new CDs with desirable antimicrobial activities. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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21 pages, 13708 KiB

Open AccessReview

Combatting Antibiotic Resistance Using Supramolecular Assemblies

by Shuwen Guo, Yuling He, Yuanyuan Zhu, Yanli Tang and Bingran Yu

Pharmaceuticals 2022, 15(7), 804; https://doi.org/10.3390/ph15070804 - 28 Jun 2022

Cited by 2 | Viewed by 2192

Abstract

Antibiotic resistance has posed a great threat to human health. The emergence of antibiotic resistance has always outpaced the development of new antibiotics, and the investment in the development of new antibiotics is diminishing. Supramolecular self-assembly of the conventional antibacterial agents has been proved to be a promising and versatile strategy to tackle the serious problem of antibiotic resistance. In this review, the recent development of antibacterial agents based on supramolecular self-assembly strategies will be introduced. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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21 pages, 3124 KiB

Open AccessReview

Photodynamic Anti-Bacteria by Carbon Dots and Their Nano-Composites

by Xiaoyan Wu, Khurram Abbas, Yuxiang Yang, Zijian Li, Antonio Claudio Tedesco and Hong Bi

Pharmaceuticals 2022, 15(4), 487; https://doi.org/10.3390/ph15040487 - 18 Apr 2022

Cited by 26 | Viewed by 3974

Abstract

The misuse of many types of broad-spectrum antibiotics leads to increased antimicrobial resistance. As a result, the development of a novel antibacterial agent is essential. Photodynamic antimicrobial chemotherapy (PACT) is becoming more popular due to its advantages in eliminating drug-resistant strains and providing broad-spectrum antibacterial resistance. Carbon dots (CDs), zero-dimensional nanomaterials with diameters smaller than 10 nm, offer a green and cost-effective alternative to PACT photosensitizers. This article reviewed the synthesis methods of antibacterial CDs as well as the recent progress of CDs and their nanocomposites in photodynamic sterilization, focusing on maximizing the bactericidal impact of CDs photosensitizers. This review establishes the base for future CDs development in the PACT field. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Nanodrugs)

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