Research

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25 pages, 9722 KiB

Open AccessArticle

Therapeutic Intervention for Various Hospital Setting Strains of Biofilm Forming Candida auris with Multiple Drug Resistance Mutations Using Nanomaterial Ag-Silicalite-1 Zeolite

by Hanan A. Aldossary, Suriya Rehman, B. Rabindran Jermy, Reem AlJindan, Afra Aldayel, Sayed AbdulAzeez, Sultan Akhtar, Firdos Alam Khan, J. Francis Borgio and Ebtesam Abdullah Al-Suhaimi

Pharmaceutics 2022, 14(10), 2251; https://doi.org/10.3390/pharmaceutics14102251 - 21 Oct 2022

Cited by 4 | Viewed by 1993

Abstract

Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist [...] Read more.

Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam, identified by 18S rRNA gene and ITS region sequencing. Drug-resistance-associated mutations in ERG11, TAC1B and FUR1 genes were screened to gain insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug-resistance-associated missense variants identified in the ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains, grouped into 3 clades. The prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial was tested against the 3 clades of clinical C. auris strains. 4wt%Ag/TiZSM-5 prepared using conventional impregnation technique was used for comparative study, and nano formulations were characterized using different techniques. The antibiofilm activity of nanomaterials was tested by cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the clades of C. auris strains, 4 wt%Ag/TiZSM-5 and Ag-silicalite-1 demonstrated a significant (p = 1.1102 × 10⁻¹⁶) inhibitory effect on the biofilm’s survival rate: the lowest inhibition value was (10%) with Ag-silicalite-1 at 24 and 48 h incubation. A profound change in morphogenesis in addition to the reduction in the number of C.auris cells was shown by SEM and light microscopy. The presence of a high surface area and the uniform dispersion of nanosized Ag species displays enhanced anti-Candida activity, and therefore it has great potential against the emerging multidrug-resistant C. auris. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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18 pages, 7662 KiB

Open AccessArticle

Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses

by Khaled AbouAitah, Abdou K. Allayh, Jacek Wojnarowicz, Yasser M. Shaker, Anna Swiderska-Sroda and Witold Lojkowski

Pharmaceutics 2021, 13(12), 2174; https://doi.org/10.3390/pharmaceutics13122174 - 16 Dec 2021

Cited by 22 | Viewed by 3123

Abstract

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that [...] Read more.

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic–organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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20 pages, 5527 KiB

Open AccessArticle

Anticandidal Potential of Two Cyanobacteria-Synthesized Silver Nanoparticles: Effects on Growth, Cell Morphology, and Key Virulence Attributes of Candida albicans

by Reham Samir Hamida, Mohamed Abdelaal Ali, Doaa A. Goda and Alya Redhwan

Pharmaceutics 2021, 13(10), 1688; https://doi.org/10.3390/pharmaceutics13101688 - 15 Oct 2021

Cited by 5 | Viewed by 2217

Abstract

Candida albicans is an opportunistic human fungal pathogen responsible for 90–100% of mucosal and nosocomial infections worldwide. The emergence of drug-resistant strains has resulted in adverse consequences for human health, including numerous deaths. Consequently, there is an urgent need to identify and develop [...] Read more.

Candida albicans is an opportunistic human fungal pathogen responsible for 90–100% of mucosal and nosocomial infections worldwide. The emergence of drug-resistant strains has resulted in adverse consequences for human health, including numerous deaths. Consequently, there is an urgent need to identify and develop new antimicrobial drugs to counter these effects. Antimicrobial nanoagents have shown potent inhibitory activity against a number of pathogens through targeting their defense systems, such as biofilm formation. Here, we investigated the anticandidal activity of silver nanoparticles biosynthesized by the cyanobacterial strains Desertifilum sp. IPPAS B-1220 and Nostoc Bahar_M (D-SNPs and N-SNPs, respectively), along with that of silver nitrate (AgNO₃), and examined the mechanisms underlying their lethal effects. For this, we performed agar well diffusion and enzyme activity assays (lactate dehydrogenase, adenosine triphosphatase, glutathione peroxidase, and catalase) and undertook morphological examinations using transmission electron microscopy. The effects of the three treatments on Hwp1 and CDR1 gene expression and protein patterns were assessed using qRT-PCR and SDS–PAGE assays, respectively. All of the three treatments inhibited C. albicans growth; disrupted membrane integrity, metabolic function, and antioxidant activity; induced ultrastructural changes in the cell envelope; and disrupted cytoplasmic and nuclear contents. Of the three agents, D-SNPs showed the greatest biocidal activity against C. albicans. Additionally, the D-SNP treatment significantly reduced the gene expression of Hwp1 and CDR1, suggestive of negative effects on biofilm formation ability and resistance potential of C. albicans, and promoted protein degradation. The mechanism involved in the biocidal effects of both D-SNPs and N-SNPs against C. albicans could be attributed to their ability to interfere with fungal cell structures and/or stimulate oxidative stress, enabling them to be used as a robust antimycotic agent. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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27 pages, 5985 KiB

Open AccessArticle

Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses

by Dhanik Reshamwala, Sailee Shroff, Olivier Sheik Amamuddy, Valentino Laquintana, Nunzio Denora, Antonella Zacheo, Vili Lampinen, Vesa P. Hytonen, Özlem Tastan Bishop, Silke Krol and Varpu Marjomäki

Pharmaceutics 2021, 13(8), 1182; https://doi.org/10.3390/pharmaceutics13081182 - 31 Jul 2021

Cited by 14 | Viewed by 3432

Abstract

To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low [...] Read more.

To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (10⁷ PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of the virions into very stable assemblies. Clustering and stabilization were not compromised even in dilute virus solutions or after diluting the polyphenols-clustered virions by 50-fold. In addition, the polyphenols lowered virus binding on cells. In silico docking experiments of these molecules against 2- and 3-fold symmetry axes of the capsid, using an algorithm developed for this study, discovered five binding sites for polyphenols, out of which three were novel binding sites. Our results altogether suggest that polyphenols exert their antiviral effect through binding to multiple sites on the virion surface, leading to aggregation of the virions and preventing RNA release and reducing cell surface binding. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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15 pages, 23075 KiB

Open AccessArticle

Development of an Immunochromatographic Strip Using Conjugated Gold Nanoparticles for the Rapid Detection of Klebsiella pneumoniae Causing Neonatal Sepsis

by Noha M. Elhosseiny, Tamer M. Samir, Aliaa A. Ali, Amani A. El-Kholy and Ahmed S. Attia

Pharmaceutics 2021, 13(8), 1141; https://doi.org/10.3390/pharmaceutics13081141 - 26 Jul 2021

Cited by 1 | Viewed by 2744

Abstract

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and [...] Read more.

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and the spread of multi-drug-resistant bacteria. In this work, we deployed bioinformatics and proteomics analyses to determine a promising target that could be used for the identification of a major neonatal sepsis causative agent, Klebsiella pneumoniae. A 19 amino acid peptide from a hypothetical outer membrane was found to be very specific to the species, well conserved among its strains, surface exposed, and expressed in conditions simulating infection. Antibodies against the selected peptide were conjugated to gold nanoparticles and incorporated into an immunochromatographic strip. The developed strip was able to detect as low as 10⁵ CFU/mL of K. pneumoniae. Regarding specificity, it showed negative results with both Escherichia coli and Enterobacter cloacae. More importantly, in a pilot study using neonatal sepsis cases blood specimens, the developed strip selectively gave positive results within 20 min with those infected with K. pneumoniae without prior sample processing. However, it gave negative results in cases infected with other bacterial species. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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Review

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26 pages, 5060 KiB

Open AccessReview

Recent Progress on Hyaluronan-Based Products for Wound Healing Applications

by Kuncham Sudhakar, Seong min Ji, Madhusudhana Rao Kummara and Sung Soo Han

Pharmaceutics 2022, 14(10), 2235; https://doi.org/10.3390/pharmaceutics14102235 - 19 Oct 2022

Cited by 9 | Viewed by 2401

Abstract

Hyaluronic acid (HA) based nanocomposites are considered excellent for improving wound healing. HA is biocompatible, biodegradable, non-toxic, biologically active, has hemostatic ability, and resists bacterial adhesion. HA-based nanocomposites promote wound healing in four different sequential phases hemostasis, inflammation, proliferation, and maturation. The unique [...] Read more.

Hyaluronic acid (HA) based nanocomposites are considered excellent for improving wound healing. HA is biocompatible, biodegradable, non-toxic, biologically active, has hemostatic ability, and resists bacterial adhesion. HA-based nanocomposites promote wound healing in four different sequential phases hemostasis, inflammation, proliferation, and maturation. The unique biological characteristics of HA enable it to serve as a drug, an antibacterial agent, and a growth factor, which combine to accelerate the healing process. In this review, we focus on the use of HA-based nanocomposites for wound healing applications and we describe the importance of HA for the wound healing process in each sequential phase, such as hemostasis, inflammation, proliferation, and maturation. Metal nanoparticles (MNPs) or metal oxide nanoparticles (MO-NPs) loaded with HA nanocomposite are used for wound healing applications. Insights into important antibacterial mechanisms are described in HA nanocomposites. Furthermore, we explain antibiotics loaded with HA nanocomposite and its combination with the MNPs/MO-NPs used for wound healing applications. In addition, HA derivatives are discussed and used in combination with the other polymers of the composite for the wound healing process, as is the role of the polymer in wound healing applications. Finally, HA-based nanocomposites used for clinical trials in animal models are presented for wound healing applications. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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24 pages, 2934 KiB

Open AccessReview

Nanotechnology in the Diagnosis and Treatment of Osteomyelitis

by Demi Zapata, Jordan Higgs, Hunter Wittholt, Kishore Chittimalli, Amanda E. Brooks and Pranothi Mulinti

Pharmaceutics 2022, 14(8), 1563; https://doi.org/10.3390/pharmaceutics14081563 - 27 Jul 2022

Cited by 3 | Viewed by 3977

Abstract

Infection remains one of the largest threats to global health. Among those infections that are especially troublesome, osteomyelitis, or inflammation of the bone, typically due to infection, is a particularly difficult condition to diagnose and treat. This difficulty stems not only from the [...] Read more.

Infection remains one of the largest threats to global health. Among those infections that are especially troublesome, osteomyelitis, or inflammation of the bone, typically due to infection, is a particularly difficult condition to diagnose and treat. This difficulty stems not only from the biological complexities of opportunistic infections designed to avoid the onslaught of both the host immune system as well as exogenous antibiotics, but also from changes in the host vasculature and the heterogeneity of infectious presentations. While several groups have attempted to classify and stage osteomyelitis, controversy remains, often delaying diagnosis and treatment. Despite a host of preclinical treatment advances being incubated in academic and company research and development labs worldwide, clinical treatment strategies remain relatively stagnant, including surgical debridement and lengthy courses of intravenous antibiotics, both of which may compromise the overall health of the bone and the patient. This manuscript reviews the current methods for diagnosing and treating osteomyelitis and then contemplates the role that nanotechnology might play in the advancement of osteomyelitis treatment. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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29 pages, 2054 KiB

Open AccessEditor’s ChoiceReview

Application of Nanomaterials in the Prevention, Detection, and Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA)

by John Hulme

Pharmaceutics 2022, 14(4), 805; https://doi.org/10.3390/pharmaceutics14040805 - 06 Apr 2022

Cited by 12 | Viewed by 3532

Abstract

Due to differences in geographic surveillance systems, chemical sanitization practices, and antibiotic stewardship (AS) implementation employed during the COVID-19 pandemic, many experts have expressed concerns regarding a future surge in global antimicrobial resistance (AMR). A potential beneficiary of these differences is the Gram-positive [...] Read more.

Due to differences in geographic surveillance systems, chemical sanitization practices, and antibiotic stewardship (AS) implementation employed during the COVID-19 pandemic, many experts have expressed concerns regarding a future surge in global antimicrobial resistance (AMR). A potential beneficiary of these differences is the Gram-positive bacteria MRSA. MRSA is a bacterial pathogen with a high potential for mutational resistance, allowing it to engage various AMR mechanisms circumventing conventional antibiotic therapies and the host’s immune response. Coupled with a lack of novel FDA-approved antibiotics reaching the clinic, the onus is on researchers to develop alternative treatment tools to mitigate against an increase in pathogenic resistance. Mitigation strategies can take the form of synthetic or biomimetic nanomaterials/vesicles employed in vaccines, rapid diagnostics, antibiotic delivery, and nanotherapeutics. This review seeks to discuss the current potential of the aforementioned nanomaterials in detecting and treating MRSA. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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37 pages, 1471 KiB

Open AccessReview

Nanotechnology Applications of Flavonoids for Viral Diseases

by Khoshnur Jannat, Alok K. Paul, Tohmina A. Bondhon, Anamul Hasan, Muhammad Nawaz, Rownak Jahan, Tooba Mahboob, Veeranoot Nissapatorn, Polrat Wilairatana, Maria de Lourdes Pereira and Mohammed Rahmatullah

Pharmaceutics 2021, 13(11), 1895; https://doi.org/10.3390/pharmaceutics13111895 - 08 Nov 2021

Cited by 22 | Viewed by 4643

Abstract

Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah [...] Read more.

Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah virus, as well as the re-emergence of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) coronaviruses. Notably, effective drugs or vaccines against these viruses are still to be discovered. All the newly approved vaccines against the SARS-CoV-2-induced disease COVID-19 possess real-time possibility of becoming obsolete because of the development of ‘variants of concern’. Flavonoids are being increasingly recognized as prophylactic and therapeutic agents against emerging and old viral diseases. Around 10,000 natural flavonoid compounds have been identified, being phytochemicals, all plant-based. Flavonoids have been reported to have lesser side effects than conventional anti-viral agents and are effective against more viral diseases than currently used anti-virals. Despite their abundance in plants, which are a part of human diet, flavonoids have the problem of low bioavailability. Various attempts are in progress to increase the bioavailability of flavonoids, one of the promising fields being nanotechnology. This review is a narrative of some anti-viral dietary flavonoids, their bioavailability, and various means with an emphasis on the nanotechnology system(s) being experimented with to deliver anti-viral flavonoids, whose systems show potential in the efficient delivery of flavonoids, resulting in increased bioavailability. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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28 pages, 3852 KiB

Open AccessReview

Application of Nanomaterials as an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases

by Jong-Woo Lim, Yu-Rim Ahn, Geunseon Park, Hyun-Ouk Kim and Seungjoo Haam

Pharmaceutics 2021, 13(10), 1570; https://doi.org/10.3390/pharmaceutics13101570 - 27 Sep 2021

Cited by 14 | Viewed by 3565

Abstract

The coronavirus disease (COVID-19) pandemic poses serious global health concerns with the continued emergence of new variants. The periodic outbreak of novel emerging and re-emerging infectious pathogens has elevated concerns and challenges for the future. To develop mitigation strategies against infectious diseases, nano-based [...] Read more.

The coronavirus disease (COVID-19) pandemic poses serious global health concerns with the continued emergence of new variants. The periodic outbreak of novel emerging and re-emerging infectious pathogens has elevated concerns and challenges for the future. To develop mitigation strategies against infectious diseases, nano-based approaches are being increasingly applied in diagnostic systems, prophylactic vaccines, and therapeutics. This review presents the properties of various nanoplatforms and discusses their role in the development of sensors, vectors, delivery agents, intrinsic immunostimulants, and viral inhibitors. Advanced nanomedical applications for infectious diseases have been highlighted. Moreover, physicochemical properties that confer physiological advantages and contribute to the control and inhibition of infectious diseases have been discussed. Safety concerns limit the commercial production and clinical use of these technologies in humans; however, overcoming these limitations may enable the use of nanomaterials to resolve current infection control issues via application of nanomaterials as a platform for the diagnosis, prevention, and treatment of viral diseases. Full article

(This article belongs to the Special Issue Nanotechnology Applied in Prevention, Diagnosis and Treatment of Infectious Diseases)

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