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Nanocarriers-Based Antimicrobial Drug Delivery

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A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 26070

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Dr. Anisha D'Souza

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Guest Editor

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA
Interests: delivery of small molecules; gene/nucleic acid delivery; development of various nano and complex delivery systems like lipid nanoparticles; polymer nanocarriers; liposomes; microparticles; lipoplexes; extracellular vesicles; transdermal delivery; stimuli-sensitive gels

Special Issue Information

Dear Colleagues,

Combating microbial infections is challenging due to the rapid development of multi-drug resistance. Microbial diseases can be contagious or infectious, resulting in short or chronic and long-lasting illnesses. Intracellular pathogens causing brucellosis, salmonellosis, tuberculosis, etc., attack the first-line mammalian defense (macrophages and non-professional phagocytes) and continue to thrive intracellularly. On the other hand, pathogens causing pneumonia, osteomyelitis and scarlet fever avoid and escape the defense line using virulent mechanisms and thrive through extracellular reproduction. Nanocarriers—polymer/lipid-based, liposomes, micelles, metal-based, silica, fullerenes, dendrimers, zeolites, quantum dots, hydrogels and composites—have been explored for antipathogenic, microbicidal, or microbiostatic properties in various microbial infections, including those arising from biofilms. Nevertheless, nanocarriers for intracellular or extracellular infections need to be designed appropriately to target specific microbes, alleviate the resistance of the drug–pathogen interaction and toxicity and disrupt biofilms as well as increase the scope in theranostics and cosmeceuticals.

In this Special Issue, manuscripts, both original research and reviews, concerning nanocarrier-based approaches for antimicrobial drug delivery-related areas of interest in human and veterinary medicine and in the food and agriculture industry are welcome.

The topics will include, but are not limited to, the following.

Medicine/pharmaceutical/drug delivery:

Nanocarriers (polymer/lipid-based, metallic and inorganic) for local treatment or selective targeting (active/passive) strategy of microbial infections.
Functionalized nanocarriers or stimuli-responsive nanocarriers for microbial therapy.
Combinatorial approach for the co-delivery of antimicrobial drugs.
Overcoming drug resistance.
Tackling biofilm-related infections.
Nanoscale antimicrobial coating on biomedical and medical devices.
Overcoming the solubility or stability issues and drug-induced side effects.
Evaluation of antimicrobial nanocarriers in vitro (characterization), preclinical and clinical models (dermal/transdermal/pulmonary/oral/other sites)—antibacterial activity studies and cytotoxicity studies.
Nano-antimicrobial in tropical infections—dengue, malaria, tuberculosis, zika, etc.

Food and Agriculture:

Active packaging of antimicrobial nanocarriers for quality and safety and applications.
Smart nano-antimicrobial food packaging.
Nanopesticides and nanoherbicides.
Environmental impact of nanocarriers used in food and agriculture.

Cosmetics/cosmeceuticals:

Antimicrobial nanocarriers in cosmetics.
Antimicrobial hair care/ skincare.

Theranostics:

Detection of antimicrobial-resistant bacterial infections using different approaches such as photo/sensitizers and multimodal imaging approaches, among others.

Dr. Anisha D'Souza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

antimicrobial nanocarriers
antimicrobial food packaging
antibiofilm
smart delivery of antimicrobials
detection of multi-drug resistance pathogens
antimicrobial resistance
metallic nanoparticles
stimuli-responsive nanocarriers
combinatorial antimicrobial delivery
nanopesticides
nanoherbicides
antimicrobials in hair care
cytotoxicity

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Published Papers (10 papers)

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Research

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15 pages, 2078 KiB

Open AccessArticle

Synergistic Antibacterial Effects of Gallate Containing Compounds with Silver Nanoparticles in Gallate Crossed Linked PVA Hydrogel Films

by John Jackson and Claudia Helena Dietrich

Antibiotics 2024, 13(4), 312; https://doi.org/10.3390/antibiotics13040312 - 29 Mar 2024

Cited by 1 | Viewed by 1602

Abstract

Currently available silver-based antiseptic wound dressings have limited patient effectiveness. There exists a need for wound dressings that behave as comfortable degradable hydrogels with a strong antibiotic potential. The objectives of this project were to investigate the combined use of gallates (either epi gallo catechin gallate (EGCG), Tannic acid, or Quercetin) as both PVA crosslinking agents and as potential synergistic antibiotics in combination with silver nanoparticles. Crosslinking was assessed gravimetrically, silver and gallate release was measured using inductively coupled plasma and HPLC methods, respectively. Synergy was measured using 96-well plate FICI methods and in-gel antibacterial effects were measured using planktonic CFU assays. All gallates crosslinked PVA with optimal extended swelling obtained using EGCG or Quercetin at 14% loadings (100 mg in 500 mg PVA with glycerol). All three gallates were synergistic in combination with silver nanoparticles against both gram-positive and -negative bacteria. In PVA hydrogel films, silver nanoparticles with EGCG or Quercetin more effectively inhibited bacterial growth in CFU counts over 24 h as compared to films containing single agents. These biocompatible natural-product antibiotics, EGCG or Quercetin, may play a dual role of providing stable PVA hydrogel films and a powerful synergistic antibiotic effect in combination with silver nanoparticles. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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13 pages, 3653 KiB

Open AccessArticle

Antibacterial Activity and Cytotoxicity Screening of Acyldepsipeptide-1 Analogues Conjugated to Silver/Indium/Sulphide Quantum Dots

by Sinazo Z. Z. Cobongela, Maya M. Makatini, Bambesiwe May, Zikhona Njengele-Tetyana, Mokae F. Bambo and Nicole R. S. Sibuyi

Antibiotics 2024, 13(2), 183; https://doi.org/10.3390/antibiotics13020183 - 13 Feb 2024

Viewed by 1964

Abstract

The continuous rise in bacterial infections and antibiotic resistance is the driving force behind the search for new antibacterial agents with novel modes of action. Antimicrobial peptides (AMPs) have recently gained attention as promising antibiotic agents with the potential to treat drug-resistant infections. Several AMPs have shown a lower propensity towards developing resistance compared to conventional antibiotics. However, these peptides, especially acyldepsipeptides (ADEPs) present with unfavorable pharmacokinetic properties, such as high toxicity and low bioavailability. Different ways to improve these peptides to be drug-like molecules have been explored, and these include using biocompatible nano-carriers. ADEP1 analogues (SC005-8) conjugated to gelatin-capped Silver/Indium/Sulfide (AgInS₂) quantum dots (QDs) improved the antibacterial activity against Gram-negative (Escherichia coli and Pseudomonas aeruginosa), and Gram-positive (Bacillus subtilis, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus) bacteria. The ADEP1 analogues exhibited minimum inhibition concentrations (MIC) between 63 and 500 µM, and minimum bactericidal concentrations (MBC) values between 125 and 750 µM. The AgInS₂-ADEP1 analogue conjugates showed enhanced antibacterial activity as evident from the MIC and MBC values, i.e., 1.6–25 µM and 6.3–100 µM, respectively. The AgInS₂-ADEP1 analogue conjugates were non-toxic against HEK-293 cells at concentrations that showed antibacterial activity. The findings reported herein could be helpful in the development of antibacterial treatment strategies. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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19 pages, 5978 KiB

Open AccessArticle

Characteristics and Antimicrobial Activities of Iron Oxide Nanoparticles Obtained via Mixed-Mode Chemical/Biogenic Synthesis Using Spent Hop (Humulus lupulus L.) Extracts

by Jolanta Flieger, Sylwia Pasieczna-Patkowska, Natalia Żuk, Rafał Panek, Izabela Korona-Głowniak, Katarzyna Suśniak, Magdalena Pizoń and Wojciech Franus

Antibiotics 2024, 13(2), 111; https://doi.org/10.3390/antibiotics13020111 - 23 Jan 2024

Cited by 6 | Viewed by 2444

Abstract

Iron oxide nanoparticles (IONPs) have many practical applications, ranging from environmental protection to biomedicine. IONPs are being investigated due to their high potential for antimicrobial activity and lack of toxicity to humans. However, the biological activity of IONPs is not uniform and depends on the synthesis conditions, which affect the shape, size and surface modification. The aim of this work is to synthesise IONPs using a mixed method, i.e., chemical co-precipitation combined with biogenic surface modification, using extracts from spent hops (Humulus lupulus L.) obtained as waste product from supercritical carbon dioxide hop extraction. Different extracts (water, dimethyl sulfoxide (DMSO), 80% ethanol, acetone, water) were further evaluated for antioxidant activity based on the silver nanoparticle antioxidant capacity (SNPAC), total phenolic content (TPC) and total flavonoid content (TFC). The IONPs were characterised via UV-vis spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS) and Fourier-transform infrared (FT-IR) spectroscopy. Spent hop extracts showed a high number of flavonoid compounds. The efficiency of the solvents used for the extraction can be classified as follows: DMSO > 80% ethanol > acetone > water. FT-IR/ATR spectra revealed the involvement of flavonoids such as xanthohumol and/or isoxanthohumol, bitter acids (i.e., humulones, lupulones) and proteins in the surface modification of the IONPs. SEM images showed a granular, spherical structure of the IONPs with diameters ranging from 81.16 to 142.5 nm. Surface modification with extracts generally weakened the activity of the IONPs against the tested Gram-positive and Gram-negative bacteria and yeasts by half. Only the modification of IONPs with DMSO extract improved their antibacterial properties against Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Bacillus cereus) from a MIC value of 2.5–10 mg/mL to 0.313–1.25 mg/mL. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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12 pages, 16456 KiB

Open AccessArticle

Chlorhexidine-Containing Electrospun Polymeric Nanofibers for Dental Applications: An In Vitro Study

by Luana Dutra de Carvalho, Bernardo Urbanetto Peres, Ya Shen, Markus Haapasalo, Hazuki Maezono, Adriana P. Manso, Frank Ko, John Jackson and Ricardo M. Carvalho

Antibiotics 2023, 12(9), 1414; https://doi.org/10.3390/antibiotics12091414 - 6 Sep 2023

Cited by 1 | Viewed by 1527

Abstract

Chlorhexidine is the most commonly used anti-infective drug in dentistry. To treat infected void areas, a drug-loaded material that swells to fill the void and releases the drug slowly is needed. This study investigated the encapsulation and release of chlorhexidine from cellulose acetate nanofibers for use as an antibacterial treatment for dental bacterial infections by oral bacteria Streptococcus mutans and Enterococcus faecalis. This study used a commercial electrospinning machine to finely control the manufacture of thin, flexible, chlorhexidine-loaded cellulose acetate nanofiber mats with very-small-diameter fibers (measured using SEM). Water absorption was measured gravimetrically, drug release was analyzed by absorbance at 254 nm, and antibiotic effects were measured by halo analysis in agar. Slow electrospinning at lower voltage (14 kV), short target distance (14 cm), slow traverse and rotation, and syringe injection speeds with controlled humidity and temperature allowed for the manufacture of strong, thin films with evenly cross-meshed, uniform low-diameter nanofibers (640 nm) that were flexible and absorbed over 600% in water. Chlorhexidine was encapsulated efficiently and released in a controlled manner. All formulations killed both bacteria and may be used to fill infected voids by swelling for intimate contact with surfaces and hold the drug in the swollen matrix for effective bacterial killing in dental settings. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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11 pages, 3192 KiB

Open AccessArticle

Lyophilized Lipid Liquid Crystalline Nanoparticles as an Antimicrobial Delivery System

by Muhammed Awad, Timothy J. Barnes and Clive A. Prestidge

Antibiotics 2023, 12(9), 1405; https://doi.org/10.3390/antibiotics12091405 - 4 Sep 2023

Viewed by 1791

Abstract

Lipid liquid crystalline nanoparticles (LCNPs) are unique nanocarriers that efficiently deliver antimicrobials through biological barriers. Yet, their wide application as an antimicrobial delivery system is hindered by their poor stability in aqueous dispersions. The production of dried LCNP powder via lyophilization is a promising approach to promote the stability of LCNPs. However, the impact of the process on the functionality of the loaded hydrophobic cargoes has not been reported yet. Herein, we investigated the potential of lyophilization to produce dispersible dry LCNPs loaded with a hydrophobic antimicrobial compound, gallium protoporphyrin (GaPP). The effect of lyophilization on the physicochemical characteristics and the antimicrobial activity of rehydrated GaPP-LCNPs was studied. The rehydrated GaPP-LCNPs retained the liquid crystalline structure and were monodisperse (PDI: 0.27 ± 0.02), with no significant change in nanoparticle concentration despite the minor increase in hydrodynamic diameter (193 ± 6.5 compared to 173 ± 4.2 prior to freeze-drying). Most importantly, the efficacy of the loaded GaPP as an antimicrobial agent and a photosensitizer was not affected as similar MIC values were obtained against S. aureus (0.125 µg/mL), with a singlet oxygen quantum yield of 0.72. These findings indicate the suitability of lyophilization to produce a dry form of LCNPs and pave the way for future studies to promote the application of LCNPs as an antimicrobial delivery system. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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12 pages, 10230 KiB

Open AccessArticle

Antibacterial Properties of the Antimicrobial Peptide Gallic Acid-Polyphemusin I (GAPI)

by Olivia Lili Zhang, John Yun Niu, Iris Xiaoxue Yin, Ollie Yiru Yu, May Lei Mei and Chun Hung Chu

Antibiotics 2023, 12(9), 1350; https://doi.org/10.3390/antibiotics12091350 - 22 Aug 2023

Cited by 7 | Viewed by 2177

Abstract

A novel antimicrobial peptide, GAPI, has been developed recently by grafting gallic acid (GA) to polyphemusin I (PI). The objective of this study was to investigate the antibacterial effects of GAPI on common oral pathogens. This laboratory study used minimum inhibitory concentrations and minimum bactericidal concentrations to assess the antimicrobial properties of GAPI against common oral pathogens. Transmission electron microscopy was used to examine the bacterial morphology both before and after GAPI treatment. The results showed that the minimum inhibitory concentration ranged from 20 μM (Lactobacillus rhamnosus) to 320 μM (Porphyromonas gingivalis), whereas the minimum bactericidal concentration ranged from 80 μM (Lactobacillus acidophilus) to 640 μM (Actinomyces naeslundii, Enterococcus faecalis, and Porphyromonas gingivalis). Transmission electron microscopy showed abnormal curvature of cell membranes, irregular cell shapes, leakage of cytoplasmic content, and disruption of cytoplasmic membranes and cell walls. In conclusion, the GAPI antimicrobial peptide is antibacterial to common oral pathogens, with the potential to be used to manage oral infections. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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18 pages, 1912 KiB

Open AccessArticle

Development, Optimization, and In Vitro/In Vivo Evaluation of Azelaic Acid Transethosomal Gel for Antidermatophyte Activity

by Ali M. Nasr, Noha M. Badawi, Yasmine H. Tartor, Nader M. Sobhy and Shady A. Swidan

Antibiotics 2023, 12(4), 707; https://doi.org/10.3390/antibiotics12040707 - 5 Apr 2023

Cited by 9 | Viewed by 2733

Abstract

Treatment of dermatophytosis is quite challenging. This work aims to investigate the antidermatophyte action of Azelaic acid (AzA) and evaluate its efficacy upon entrapment into transethosomes (TEs) and incorporation into a gel to enhance its application. Optimization of formulation variables of TEs was carried out after preparation using the thin film hydration technique. The antidermatophyte activity of AzA-TEs was first evaluated in vitro. In addition, two guinea pig infection models with Trichophyton (T.) mentagrophytes and Microsporum (M.) canis were established for the in vivo assessment. The optimized formula showed a mean particle size of 219.8 ± 4.7 nm and a zeta potential of −36.5 ± 0.73 mV, while the entrapment efficiency value was 81.9 ± 1.4%. Moreover, the ex vivo permeation study showed enhanced skin penetration for the AzA-TEs (3056 µg/cm²) compared to the free AzA (590 µg/cm²) after 48 h. AzA-TEs induced a greater inhibition in vitro on the tested dermatophyte species than free AzA (MIC₉₀ was 0.01% vs. 0.32% for T. rubrum and 0.032% for T. mentagrophytes and M. canis vs. 0.56%). The mycological cure rate was improved in all treated groups, specially for our optimized AzA-TEs formula in the T. mentagrophytes model, in which it reached 83% in this treated group, while it was 66.76% in the itraconazole and free AzA treated groups. Significant (p < 0.05) lower scores of erythema, scales, and alopecia were observed in the treated groups in comparison with the untreated control and plain groups. In essence, the TEs could be a promising carrier for AzA delivery into deeper skin layers with enhanced antidermatophyte activity. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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Review

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25 pages, 1786 KiB

Open AccessReview

From Polymeric Nanoformulations to Polyphenols—Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin

by Ance Bārzdiņa, Aiva Plotniece, Arkadij Sobolev, Karlis Pajuste, Dace Bandere and Agnese Brangule

Antibiotics 2024, 13(4), 305; https://doi.org/10.3390/antibiotics13040305 - 28 Mar 2024

Cited by 3 | Viewed by 2642

Abstract

Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin. In addition, factors influencing the synthesis of gentamicin-loaded polymeric (poly (lactic-co-glycolic acid) (PLGA) and chitosan) nanoparticles and the methods used in drug release studies are discussed. Potential research directions and future perspectives for gentamicin-loaded drug delivery systems are given. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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18 pages, 1762 KiB

Open AccessReview

Innovative Approaches for Maintaining and Enhancing Skin Health and Managing Skin Diseases through Microbiome-Targeted Strategies

by Khadeejeh AL-Smadi, Vania Rodrigues Leite-Silva, Newton Andreo Filho, Patricia Santos Lopes and Yousuf Mohammed

Antibiotics 2023, 12(12), 1698; https://doi.org/10.3390/antibiotics12121698 - 4 Dec 2023

Cited by 8 | Viewed by 6304

Abstract

The skin microbiome is crucial in maintaining skin health, and its disruption is associated with various skin diseases. Prebiotics are non-digestible fibers and compounds found in certain foods that promote the activity and growth of beneficial bacteria in the gut or skin. On the other hand, live microorganisms, known as probiotics, benefit in sustaining healthy conditions when consumed in reasonable quantities. They differ from postbiotics, which are by-product compounds from bacteria that release the same effects as their parent bacteria. The human skin microbiome is vital when it comes to maintaining skin health and preventing a variety of dermatological conditions. This review explores novel strategies that use microbiome-targeted treatments to maintain and enhance overall skin health while managing various skin disorders. It is important to understand the dynamic relationship between these beneficial microorganisms and the diverse microbial communities present on the skin to create effective strategies for using probiotics on the skin. This understanding can help optimize formulations and treatment regimens for improved outcomes in skincare, particularly in developing solutions for various skin problems. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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21 pages, 2144 KiB

Open AccessReview

Inorganic Nanoparticles: Tools to Emphasize the Janus Face of Amphotericin B

by Ariane Boudier, Nour Mammari, Emmanuel Lamouroux and Raphaël E. Duval

Antibiotics 2023, 12(10), 1543; https://doi.org/10.3390/antibiotics12101543 - 15 Oct 2023

Viewed by 1651

Abstract

Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice, in particular for the treatment of invasive diseases, even though it is not devoid of side effects (particularly nephrotoxicity). Recently, its redox properties (i.e., both prooxidant and antioxidant) have been highlighted in the literature as mechanisms involved in both its activity and its toxicity. Interestingly, similar properties can be described for inorganic nanoparticles. In the first part of the present review, the redox properties of Amphotericin B and inorganic nanoparticles are discussed. Then, in the second part, inorganic nanoparticles as carriers of the drug are described. A special emphasis is given to their combined redox properties acting either as a prooxidant or as an antioxidant and their connection to the activity against pathogens (i.e., fungi, parasites, and yeasts) and to their toxicity. In a majority of the published studies, inorganic nanoparticles carrying Amphotericin B are described as having a synergistic activity directly related to the rupture of the redox homeostasis of the pathogen. Due to the unique properties of inorganic nanoparticles (e.g., magnetism, intrinsic anti-infectious properties, stimuli-triggered responses, etc.), these nanomaterials may represent a new generation of medicine that can synergistically enhance the antimicrobial properties of Amphotericin B. Full article

(This article belongs to the Special Issue Nanocarriers-Based Antimicrobial Drug Delivery)

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