Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers

Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics.

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Mining a Nanoparticle Dataset, Compiled Within the MODENA-COST Action

Research Anthology on Synthesis, Characterization, and Applications of Nanomaterials ◽

10.4018/978-1-7998-8591-7.ch071 ◽

2021 ◽

pp. 1706-1724

Author(s):

Sabine Van Miert ◽

Jan Creylman ◽

Geert R. Verheyen

Keyword(s):

Chemical Properties ◽

In Vitro Testing ◽

Cost Action ◽

Robust Model ◽

Physico Chemical ◽

Classification And Regression ◽

Toxic Potential ◽

Sheer Number

Engineered nanomaterials (ENM) have new or enhanced physico-chemical properties compared to their micron-sized counterparts, but may also have an increased toxic potential. Animal and in vitro testing are typically employed to investigate the toxic effects of (nano)materials. The sheer number of ENMs and their physico-chemical parameters make it impossible to only use in vivo and in vitro testing, and modelling technologies are also deployed to find relationships between ENM parameters and toxicity. A heterogenous dataset containing information on 192 nanoparticle endpoints was compiled within the MODENA COST-Action consortium. Here, the available data was mined to identify relationships between nanoparticle properties and cell-death as measured with four cytotoxicity assays. ANOVA, collinearity analyses and classification and regression trees gave indications on potential relations between the NP-properties and toxicity, but could not deliver a robust model. More information and datapoints are necessary to build well-validated models.

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Synthetic Peptides as a Promising Alternative to Control Viral Infections in Atlantic Salmon

Pathogens ◽

10.3390/pathogens9080600 ◽

2020 ◽

Vol 9 (8) ◽

pp. 600 ◽

Cited By ~ 1

Author(s):

Constanza Cárdenas ◽

Fanny Guzmán ◽

Marisela Carmona ◽

Cristian Muñoz ◽

Luis Nilo ◽

...

Keyword(s):

Viral Load ◽

Viral Infections ◽

Antiviral Agents ◽

In Silico Analysis ◽

Infectious Pancreatic Necrosis Virus ◽

Fish Cell ◽

Promising Alternative ◽

Anemia Virus

Viral infections in salmonids represent an ongoing challenge for the aquaculture industry. Two RNA viruses, the infectious pancreatic necrosis virus (IPNV) and the infectious salmon anemia virus (ISAV), have become a latent risk without healing therapies available for either. In this context, antiviral peptides emerge as effective and relatively safe therapeutic molecules. Based on in silico analysis of VP2 protein from IPNV and the RNA-dependent RNA polymerase from ISAV, a set of peptides was designed and were chemically synthesized to block selected key events in their corresponding infectivity processes. The peptides were tested in fish cell lines in vitro, and four were selected for decreasing the viral load: peptide GIM182 for IPNV, and peptides GIM535, GIM538 and GIM539 for ISAV. In vivo tests with the IPNV GIM 182 peptide were carried out using Salmo salar fish, showing a significant decrease of viral load, and proving the safety of the peptide for fish. The results indicate that the use of peptides as antiviral agents in disease control might be a viable alternative to explore in aquaculture.

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In Vitro Physico-Chemical Characterization and Standardized In Vivo Evaluation of Biocompatibility of a New Synthetic Membrane for Guided Bone Regeneration

Materials ◽

10.3390/ma12071186 ◽

2019 ◽

Vol 12 (7) ◽

pp. 1186

Author(s):

Lívia da Costa Pereira ◽

Carlos Fernando de Almeida Barros Mourão ◽

Adriana Terezinha Neves Novellino Alves ◽

Rodrigo Figueiredo de Brito Resende ◽

Marcelo José Pinheiro Guedes de Uzeda ◽

...

Keyword(s):

Bone Regeneration ◽

Chemical Properties ◽

Chemical Characterization ◽

Guided Bone Regeneration ◽

Tissue Reaction ◽

In Vivo Evaluation ◽

Physico Chemical ◽

Tissue Reactions

This study’s aim was to evaluate the biocompatibility and bioabsorption of a new membrane for guided bone regeneration (polylactic-co-glycolic acid associated with hydroxyapatite and β-tricalcium phosphate) with three thicknesses (200, 500, and 700 µm) implanted in mice subcutaneously. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and the quantification of carbon, hydrogen and nitrogen were used to characterize the physico-chemical properties. One hundred Balb-C mice were divided into 5 experimental groups: Group 1—Sham (without implantation); Group 2—200 μm; Group 3—500 μm; Group 4—700 μm; and Group 5—Pratix®. Each group was subdivided into four experimental periods (7, 30, 60 and 90 days). Samples were collected and processed for histological and histomorphometrical evaluation. The membranes showed no moderate or severe tissue reactions during the experimental periods studied. The 500-μm membrane showed no tissue reaction during any experimental period. The 200-μm membrane began to exhibit fragmentation after 30 days, while the 500-μm and 700-µm membranes began fragmentation at 90 days. All membranes studied were biocompatible and the 500 µm membrane showed the best results for absorption and tissue reaction, indicating its potential for clinical guided bone regeneration.

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Redox Sensitive Polysaccharide Based Nanoparticles for Improved Cancer Treatment: A Comprehensive Review

Current Pharmaceutical Design ◽

10.2174/1381612824666180813114841 ◽

2018 ◽

Vol 24 (28) ◽

pp. 3303-3319 ◽

Cited By ~ 4

Author(s):

Erfaneh Ghassami ◽

Jaleh Varshosaz ◽

Somayeh Taymouri

Keyword(s):

Drug Delivery ◽

Cancer Treatment ◽

Drug Delivery Systems ◽

Chemical Properties ◽

Delivery Systems ◽

Exchange Reactions ◽

Triggered Release ◽

Redox Responsive

Background: Among the numerous bio-responsive polymeric drug delivery systems developed recently, redox-triggered release of molecular payloads have gained great deal of attention, especially in the field of anticancer drug delivery. In most cases, these systems rely on disulfide bonds located either in the matrix crosslinks, or in auxiliary chains to achieve stimuli-responsive drug release. These bonds keep their stability in extracellular environments, yet, rapidly break by thiol–disulfide exchange reactions in the cytosol, due to the presence of greater levels of glutathione. Polysaccharides are macromolecules with low cost, natural abundance, biocompatibility, biodegradability, appropriate physical and chemical properties, and presence of numerous functional groups which facilitate chemical or physical cross-linking. Methods: With regards to the remarkable advantages of polysaccharides, in the current study, various polysaccharide-based redox-responsive drug delivery systems are reviewed. In most cases the in vitro/in vivo effects of the developed system were also evaluated. Results: Considering the hypoxic and reducing nature of the tumor microenvironment, with several folds higher glutathione levels than the systemic tissues, redox-sensitive polymeric systems could be implemented for tumorspecific drug delivery and the results of the previous researches in this field indicated satisfactory achievements. Conclusion: According to the reviewed papers, the efficiency of diverse redox-responsive polysaccharide-based nanoparticles with therapeutic payloads in cancer chemotherapy could be concluded. Nevertheless, more comprehensive studies are required to understand the exact intracellular and systemic fate of these nano-carriers, as well as their clinical efficacy for cancer treatment.

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Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis

Pharmaceutics ◽

10.3390/pharmaceutics11060263 ◽

2019 ◽

Vol 11 (6) ◽

pp. 263 ◽

Cited By ~ 4

Author(s):

Maria Letizia Manca ◽

Iris Usach ◽

José Esteban Peris ◽

Antonella Ibba ◽

Germano Orrù ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Chemical Properties ◽

Chemical Characterization ◽

Yeast Cells ◽

Unilamellar Vesicles ◽

Transmission Electron ◽

Physico Chemical

New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.

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Potential Applications of Biphosphonates in Dental Surgical Implants

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200702000304 ◽

2007 ◽

Vol 20 (3) ◽

pp. 455-465 ◽

Cited By ~ 6

Author(s):

D. Berardi ◽

T. Carlesi ◽

F. Rossi ◽

M. Calderini ◽

R. Volpi ◽

...

Keyword(s):

Alveolar Bone ◽

Chemical Properties ◽

Osteonecrosis Of The Jaw ◽

In Vivo Experiments ◽

Surgical Implants ◽

Physico Chemical ◽

Potential Applications ◽

Collateral Effect

Biphosphonates are largely used for their unquestionable properties of inhibiting bone resorption by osteoclast in the treatment of various osteometabolic illnesses such as osteoporosis, multiple myeloma, tumors which metastasize to the bone and malignant hypercalcemia. In this literature review the physico-chemical properties, biologic activities and the mechanisms of action of biphosphonates are described. The use of these drugs is discussed, analyzing the quantity of results which have emerged through in vitro and in vivo experiments on animal models. In this study the efficiency of these drugs is demonstrated in contrasting the osteolitic processes of the alveolar bone, in promoting the neoformation and in bettering the quality of bone implants. However, it is important to draw attention to a worrying correlation which has emerged during the last 3–4 years, between osteonecrosis of the jaw (ONJ) and the systemic administration of aminobiphosphonates. This collateral effect did not emerge following the use of non-aminobiphosphonates. The aim of this revie w is to identify the guidelines for the use of biphosphonates in oral implant surgery.

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A Critical Review on Nanoscience Advancement: In Treatment of Viral Infection

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i6.5030 ◽

2021 ◽

Vol 11 (6) ◽

pp. 225-237

Author(s):

Kajal Chaudhary ◽

Shweta Parihar ◽

Devender Sharma

Keyword(s):

Drug Delivery ◽

Physicochemical Properties ◽

Viral Infection ◽

Viral Infections ◽

Antiviral Treatment ◽

Antiviral Drug ◽

Chemical Properties ◽

Design Factor ◽

Antiviral Medications ◽

Virus Influenza

Viral contaminations speak to a general medical issue and one of the main sources of worldwide mortality. A large portion of the antiviral medications have low permeability, low dissolvability and other related physical properties which make them less efficient for the antiviral treatment. To conquer these constraints, different nanomedicine stages have been planned. Nanomaterials offer special physico-chemical properties that have various advantages for medicate conveyance as perfect devices for viral treatment. This review focuses on the currently used medicines used in viral infection, presents a broad overview of the application of nanosized materials for the treatment of common viral infections and shed light on the potential of nanotechnology to provide more effective treatment for HIV, Herpes simplex virus, Influenza virus and Hepatitis C virus. The action of antiviral medications could be improved with nanomedicine formulations. As the physicochemical properties of nanocarriers can empower their capacity to target the specific sites. When it comes to structuring nanocarriers, size is the most important factor and the nanoparticles can permit the controlled delivery kinetics, enhanced bioavailability, altered pharmacokinetics, and less side effects. Nanocarriers that build them appealing candidates for antiviral drug such as Improves bioavailability of the encapsulated actives, controlled release, reduce the toxicity associated with the anti-viral drugs. One of the important physicochemical properties mainly size is the most important design factor for nanocarriers for anti-viral drug delivery to the specific sites. Nanobased drug delivery also leads to enhance the potential of currently approved antiviral drugs. Keywords: Nanotechnology, HIV, Hepatits virus, Influenza, HSV

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Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

10.1101/2020.05.22.109900 ◽

2020 ◽

Cited By ~ 1

Author(s):

Xi Yu ◽

Liming Zhang ◽

Liangqin Tong ◽

Nana Zhang ◽

Han Wang ◽

...

Keyword(s):

Broad Spectrum ◽

Lipase Activity ◽

Antiviral Agents ◽

Antiviral Drug ◽

Viral Envelope ◽

Global Public Health ◽

Virucidal Activity ◽

Extracellular Milieu

AbstractViruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.

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The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity

Nanomaterials ◽

10.3390/nano10081508 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1508

Author(s):

Danica Jović ◽

Vesna Jaćević ◽

Kamil Kuča ◽

Ivana Borišev ◽

Jasminka Mrdjanovic ◽

...

Keyword(s):

Carbon Nanomaterials ◽

Wide Spectrum ◽

Chemical Properties ◽

Carbon Nanomaterial ◽

In Vivo Models ◽

Physico Chemical ◽

The Impact ◽

Cell Signaling Pathways

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.

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