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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 75517

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Prof. Dr. Franco Dosio

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Guest Editor

Department of Drug Science and Technology, University of Torino, Turin, Italy
Interests: nanotechnology in drug delivery; targeted drug delivery; liposomes; polymeric nanoparticles; self-assembling nanosystems; anticancer agents; antimicrobial agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious disease still represents a significant challenge in health care, being one of the major causes of mortality in the world. In addition, the use of many conventional drugs is hampered by a lack of efficacy, emergence of resistance, adverse effects, and high costs. In this context, nanotechnology plays a key role in improving the efficacy of existing drugs by the use of nanoengineered drug delivery systems. Nevertheless, other relevant applications of nanoparticles are found in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, as well as in bacterial detection systems. This Special Issue is aimed at covering recent advances in the synthesis, assembly, mechanistic understanding and uses of nanotechnology applied to the development of novel systems for the prevention, detection and treatment of microbial infections.

Several classes of antimicrobial nanosystems are discussed:

Antibacterial polymers

Antimicrobial drug delivery systems

Inorganic-polymer hybrid nanoparticles

Antibacterial coating

Prof. Franco Dosio
Guest Editor

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Keywords

Polymer nanoparticles
Antimicrobial agents
Antimicrobial resistance
Inorganic nanosystems

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Published Papers (10 papers)

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Research

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11 pages, 1326 KiB

Open AccessFeature PaperArticle

Electrochemical Preparation of Synergistic Nanoantimicrobials

by Maria Chiara Sportelli, Daniela Longano, Elisabetta Bonerba, Giuseppina Tantillo, Luisa Torsi, Luigia Sabbatini, Nicola Cioffi and Nicoletta Ditaranto

Molecules 2020, 25(1), 49; https://doi.org/10.3390/molecules25010049 - 22 Dec 2019

Cited by 16 | Viewed by 3424

Abstract

The rapid spreading of resistance among common bacterial pathogens towards the misused antibiotics/disinfectant agents has drawn much attention worldwide to bacterial infections. In light of this, the present work aimed at the realization of core–shell nanoparticles possessing remarkable antimicrobial properties thanks to the synergistic action of the metal core and the disinfectant shell. Copper nanoparticles stabilized by benzalkonium chloride were prepared, characterized, and implemented in poly-vinyl-methyl ketone to obtain nanoantimicrobial composite coatings. Bioactivity tests are reported, proving the excellent disinfectant properties of the proposed nanomaterials, as compared to one of the well-known and strongest silver-based nanoantimicrobials. Applications are also briefly described. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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15 pages, 3646 KiB

Open AccessArticle

Preparation and Application of Bioshell Calcium Oxide (BiSCaO) Nanoparticle-Dispersions with Bactericidal Activity

by Yoko Sato, Masayuki Ishihara, Shingo Nakamura, Koichi Fukuda, Tomohiro Takayama, Sumiyo Hiruma, Kaoru Murakami, Masanori Fujita and Hidetaka Yokoe

Molecules 2019, 24(18), 3415; https://doi.org/10.3390/molecules24183415 - 19 Sep 2019

Cited by 20 | Viewed by 3881

Abstract

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO₂⁻ and NO₃⁻. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na₃PO₄, Na₂HPO₄ or NaH₂PO₄ and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO₂⁻ and NO₃⁻ after mixing BiSCaO dispersion and pure water containing a high proportion of NO₂⁻ and NO₃⁻ were measured. BiSCaO dispersion formed with Na₂HPO₄, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)₂, which was mainly composed of Ca(OH)₂. BiSCaO, but not SSP-Ca(OH)₂, could reduce the concentration of NO₂⁻ and NO₃⁻ by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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10 pages, 7037 KiB

Open AccessFeature PaperArticle

Preparation of Sesquiterpene Lactone-Loaded PLA Nanoparticles and Evaluation of Their Antitrypanosomal Activity

by Njogu M. Kimani, Solveig Backhaus, Josphat C. Matasyoh, Marcel Kaiser, Fabian C. Herrmann, Thomas J. Schmidt and Klaus Langer

Molecules 2019, 24(11), 2110; https://doi.org/10.3390/molecules24112110 - 4 Jun 2019

Cited by 10 | Viewed by 3420

Abstract

Human African trypanosomiasis (HAT), also commonly known as sleeping sickness, is a neglected tropical disease affecting millions of people in poorly developed regions in sub-Saharan Africa. There is no satisfactory treatment for this infection. The investment necessary to bring new drugs to the market is a big deterrent to drug development, considering that the affected communities form a non-lucrative sector. However, natural products and many sesquiterpene lactones (STLs) in particular are very strong trypanocides. Research and applications of nano-drug delivery systems such as nanoparticles (NPs) have undergone unprecedented growth in the recent past. This is mainly due to the advantages offered by these systems, such as targeted delivery of the drug to the place of action (cell, parasite, etc), sustained release of the drug, increased bioavailability, reduced drug dosage, and reduction of undesired side effects, among others. In this study, the STLs α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, all trypanocides, were loaded into polylactic acid (PLA) NPs through an emulsification-diffusion method. The NPs were stable, homogenous, and spherical in shape with a rounded knotty depression like a navel orange. The average particle sizes were 202.3, 220.3, 219.5, 216.9, and 226.4 nm for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs had encapsulation efficiencies of 94.6, 78.1, 76.8, 60.7, and 78.9% for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs loaded with arglabin, vernolepin, and eucannabinolide exhibited considerable antitrypanosomal activity against Trypanosoma brucei rhodesiense (Tbr) with free drug equivalent IC₅₀ values of 3.67, 1.11 and 3.32 µM, respectively. None of the NP formulations displayed cytotoxicity towards mammalian cells (rat skeletal myoblast cell line L6). These results provide new insights into the possibility of incorporating STLs into nanoparticles, which may provide new options for their formulation in order to develop new drugs against HAT. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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12 pages, 946 KiB

Open AccessArticle

Silver(I) Complexes of the Pharmaceutical Agents Metronidazole and 4-Hydroxymethylpyridine: Comparison of Cytotoxic Profile for Potential Clinical Application

by Lidia Radko, Sylwia Stypuła-Trębas, Andrzej Posyniak, Dominik Żyro and Justyn Ochocki

Molecules 2019, 24(10), 1949; https://doi.org/10.3390/molecules24101949 - 21 May 2019

Cited by 32 | Viewed by 4614

Abstract

In previous papers, we have reported on the high antifungal and significant antibacterial activity against Gram-positive and Gram-negative bacteria of the water-soluble silver(I) complexes of metronidazole and derivatives of pyridine compared to silver nitrate. In the present study, the cytotoxic activity of the silver(I) complexes of metronidazole and 4-hydroxymethylpyridine was compared with that of silver nitrate. Metronidazole and 4-hydroxymethylpyridine were investigated using Balb/c 3T3 and HepG2 cell lines in order to evaluate the potential clinical application of silver(I) complexes. The cells were exposed for 72 h to compounds at eight concentrations. The cytotoxic concentrations (IC₅₀) of the study compounds were assessed within four biochemical endpoints: mitochondrial activity, lysosomal activity, cellular membrane integrity, and total protein content. The investigated silver(I) complexes displayed comparable cytotoxicity to that of silver nitrate used in clinics. Mean cytotoxic concentrations calculated for investigated silver(I) complexes from concentration–response curves ranged from 2.13 to 26.5 µM. HepG2 cells were less sensitive to the tested complexes compared to fibroblasts (Balb/c 3T3). However, the most affected endpoint for HepG2 cells was cellular membrane damage. The cytotoxicity of both silver complexes was comparable for Balb/c 3T3 cells. The cytotoxic potential of the new silver(I) compounds compared to that of silver nitrate used in medicine indicates that they are safe and could be used in clinical practice. The presented results are yet more stimulating to further studies that evaluate the therapeutic use of silver complexes. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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18 pages, 6363 KiB

Open AccessArticle

Bacteria Death and Osteoblast Metabolic Activity Correlated to Hydrothermally Synthesised TiO₂ Surface Properties

by Alka Jaggessar, Asha Mathew, Tuquabo Tesfamichael, Hongxia Wang, Cheng Yan and Prasad KDV Yarlagadda

Molecules 2019, 24(7), 1201; https://doi.org/10.3390/molecules24071201 - 27 Mar 2019

Cited by 27 | Viewed by 3559

Abstract

Orthopaedic surgery comes with an inherent risk of bacterial infection, prolonged antibiotic therapy and revision surgery. Recent research has focused on nanostructured surfaces to improve the bactericidal and osseointegrational properties of implants. However, an understanding of the mechanical properties of bactericidal materials is lacking. In this work, the surface properties of hydrothermal TiO₂ nanostructured surfaces are investigated for their effect on bactericidal efficiency and cellular metabolic activity of human osteoblast cells. TiO₂ nanostructures, approximately 307 nm in height and 14 GPa stiffness, were the most effective structures against both gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa) bacteria. Statistical analysis significantly correlated structure height to the death of both bacteria strains. In addition, the surface contact angle and Young’s modulus were correlated to osteoblast metabolic activity. Hydrophilic surfaces with a contact angle between 35 and 50° produced the highest cellular metabolic activity rates after 24 h of incubation. The mechanical tests showed that nanostructures retain their mechanical stability and integrity over a long time-period, reaffirming the surfaces’ applicability for implants. This work provides a thorough examination of the surface, mechanical and wettability properties of multifunctional hydrothermally synthesised nanostructured materials, capable of killing bacteria whilst improving osteoblast metabolic rates, leading to improved osseointegration and antibacterial properties of orthopaedic implants. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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Review

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24 pages, 1024 KiB

Open AccessReview

Ozonated Oils as Antimicrobial Systems in Topical Applications. Their Characterization, Current Applications, and Advances in Improved Delivery Techniques

by Elena Ugazio, Vivian Tullio, Arianna Binello, Silvia Tagliapietra and Franco Dosio

Molecules 2020, 25(2), 334; https://doi.org/10.3390/molecules25020334 - 14 Jan 2020

Cited by 90 | Viewed by 16043

Abstract

The search for a wide spectrum of antimicrobial agents that can avoid resistance while maintaining reasonable side effects has led to ozonated oils experiencing an increase in scientific interest and clinical applications. The treatment of vegetable oils with ozone leads to the creation of a reservoir of ozone that slowly releases into the skin thanks to the fact that ozone can be held as ozonides of unsaturated fatty acids. Interest in the use of ozonated oils has meant that several ozonated-vegetable-oil-containing products have been commercialized as cosmetic and pharmaceutical agents, and in innovative textile products with antibacterial activity. New approaches to the delivery of ozonated oils have very recently appeared in an attempt to improve their characteristics and reduce drawbacks, such as an unpleasant odor, high viscosity and undesired effects on skin, including irritation and rashes. The present review focuses on the current status of delivery agents that use ozonated oils as antimicrobial agents in topical (dermal, skin, and soft tissues) treatments. Challenges and future opportunities for these delivery systems will also be discussed. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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15 pages, 734 KiB

Open AccessReview

Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles

by Roberto Canaparo, Federica Foglietta, Francesca Giuntini, Carlo Della Pepa, Franco Dosio and Loredana Serpe

Molecules 2019, 24(10), 1991; https://doi.org/10.3390/molecules24101991 - 24 May 2019

Cited by 152 | Viewed by 8182

Abstract

Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a number of future prospects. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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17 pages, 1782 KiB

Open AccessReview

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

by Jiajia Hong, Xuemei Lu, Zhixiong Deng, Shufeng Xiao, Bing Yuan and Kai Yang

Molecules 2019, 24(9), 1775; https://doi.org/10.3390/molecules24091775 - 7 May 2019

Cited by 73 | Viewed by 8415

Abstract

Antimicrobial peptides (AMPs), as a key component of the immune defense systems of organisms, are a promising solution to the serious threat of drug-resistant bacteria to public health. As one of the most representative and extensively studied AMPs, melittin has exceptional broad-spectrum activities against microorganisms, including both Gram-positive and Gram-negative bacteria. Unfortunately, the action mechanism of melittin with bacterial membranes, especially the underlying physics of peptide-induced membrane poration behaviors, is still poorly understood, which hampers efforts to develop melittin-based drugs or agents for clinical applications. In this mini-review, we focus on recent advances with respect to the membrane insertion behavior of melittin mostly from a computational aspect. Membrane insertion is a prerequisite and key step for forming transmembrane pores and bacterial killing by melittin, whose occurrence is based on overcoming a high free-energy barrier during the transition of melittin molecules from a membrane surface-binding state to a transmembrane-inserting state. Here, intriguing simulation results on such transition are highlighted from both kinetic and thermodynamic aspects. The conformational changes and inter-peptide cooperation of melittin molecules, as well as melittin-induced disturbances to membrane structure, such as deformation and lipid extraction, are regarded as key factors influencing the insertion of peptides into membranes. The associated intermediate states in peptide conformations, lipid arrangements, membrane structure, and mechanical properties during this process are specifically discussed. Finally, potential strategies for enhancing the poration ability and improving the antimicrobial performance of AMPs are included as well. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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30 pages, 2138 KiB

Open AccessReview

Antimicrobial Nanoparticles Incorporated in Edible Coatings and Films for the Preservation of Fruits and Vegetables

by Yage Xing, Wenxiu Li, Qin Wang, Xuanlin Li, Qinglian Xu, Xunlian Guo, Xiufang Bi, Xiaocui Liu, Yuru Shui, Hongbin Lin and Hua Yang

Molecules 2019, 24(9), 1695; https://doi.org/10.3390/molecules24091695 - 30 Apr 2019

Cited by 107 | Viewed by 10570

Abstract

Edible coatings and films (ECF) are employed as matrixes for incorporating antimicrobial nanoparticles (NPs), and then they are applied on the fruits and vegetables to prolong shelf life and enhance storage quality. This paper provides a comprehensive review on the preparation, antimicrobial properties and mechanisms, surface and physical qualities of ECF containing antimicrobial NPs, and its efficient application to vegetables and fruits as well. Following an introduction on the properties of the main edible coating materials, the preparation technologies of ECF with NPs are summarized. The antimicrobial activity of ECF with NPs against the tested microorganism was observed by many researchers. This might be mainly due to the electrostatic interaction between the cationic polymer or free metal ions and the charged cell membrane, the photocatalytic reaction of NPs, the detachment of free metal ion, and partly due to the antimicrobial activity of edible materials. Moreover, their physical, mechanical and releasing properties are discussed in detail, which might be influenced by the concentration of NPs. The preservation potential on the quality of fruits and vegetables indicates that various ECF with NPs might be used as the ideal materials for food application. Following the introduction on these characteristics, an attempt is made to predict future trends in this field. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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15 pages, 532 KiB

Open AccessReview

Application of Antimicrobial Nanoparticles in Dentistry

by Wenjing Song and Shaohua Ge

Molecules 2019, 24(6), 1033; https://doi.org/10.3390/molecules24061033 - 15 Mar 2019

Cited by 162 | Viewed by 12507

Abstract

Oral cavity incessantly encounters a plethora of microorganisms. Plaque biofilm—a major cause of caries, periodontitis and other dental diseases—is a complex community of bacteria or fungi that causes infection by protecting pathogenic microorganisms from external drug agents and escaping the host defense mechanisms. Antimicrobial nanoparticles are promising because of several advantages such as ultra-small sizes, large surface-area-to-mass ratio and special physical and chemical properties. To better summarize explorations of antimicrobial nanoparticles and provide directions for future studies, we present the following critical review. The keywords “nanoparticle,” “anti-infective or antibacterial or antimicrobial” and “dentistry” were retrieved from Pubmed, Scopus, Embase and Web of Science databases in the last five years. A total of 172 articles met the requirements were included and discussed in this review. The results show that superior antibacterial properties of nanoparticle biomaterials bring broad prospects in the oral field. This review presents the development, applications and underneath mechanisms of antibacterial nanoparticles in dentistry including restorative dentistry, endodontics, implantology, orthodontics, dental prostheses and periodontal field. Full article

(This article belongs to the Special Issue Frontiers of Antimicrobial Nanoparticles)

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