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1.
ACS Appl Mater Interfaces ; 14(1): 49-56, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1608662

ABSTRACT

The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents. This coating minimally impacts the mechanical properties of the fabric while also imparting hydrophobicity. Passive inactivation of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) is achieved with >98% inactivation after 24 h, with a 23× and 3× inactivation rate increase against E. coli and MRSA, respectively, when green light is used to generate ROS. Up to 90% decrease in the infectivity of SARS-CoV-2 after 2 h of irradiated incubation with the material is demonstrated. These results show that modifying textiles with dual-functional polymers results in robust and highly antimicrobial materials that are expected to find widespread use in combating the spread of deadly pathogens.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Coated Materials, Biocompatible/chemistry , Polymers/chemistry , SARS-CoV-2/drug effects , Textiles/analysis , Anti-Infective Agents/chemistry , COVID-19/prevention & control , COVID-19/virology , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Textiles/toxicity , Ultraviolet Rays
2.
Int J Mol Sci ; 22(24)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580689

ABSTRACT

Global reports on multidrug resistance (MDR) and life-threatening pathogens such as SARS-CoV-2 and Candida cruris have stimulated researchers to explore new antimicrobials that are eco-friendly and economically viable. In this context, biodegradable polymers such as nisin, chitin, and pullulan play an important role in solving the problem. Pullulan is an important edible, biocompatible, water-soluble polymer secreted by Aureobasidium pullulans that occurs ubiquitously. It consists of maltotriose units linked with α-1,6 glycosidic bonds and is classed as Generally Regarded as Safe (GRAS) by the Food and Drug Administration (FDA) in the USA. Pullulan is known for its antibacterial, antifungal, antiviral, and antitumor activities when incorporated with other additives such as antibiotics, drugs, nanoparticles, and so on. Considering the importance of its antimicrobial activities, this polymer can be used as a potential antimicrobial agent against various pathogenic microorganisms including the multidrug-resistant (MDR) pathogens. Moreover, pullulan has ability to synthesize biogenic silver nanoparticles (AgNPs), which are remarkably efficacious against pathogenic microbes. The pullulan-based nanocomposites can be applied for wound healing, food packaging, and also enhancing the shelf-life of fruits and vegetables. In this review, we have discussed biosynthesis of pullulan and its role as antibacterial, antiviral, and antifungal agent. Pullulan-based films impregnated with different antimicrobials such as AgNPs, chitosan, essential oils, and so on, forming nanocomposites have also been discussed as natural alternatives to combat the problems posed by pathogens.


Subject(s)
Anti-Infective Agents/pharmacology , Drug Resistance, Multiple/drug effects , Glucans/biosynthesis , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Antifungal Agents , COVID-19 , Chitin/pharmacology , Chitosan/chemistry , Drug Resistance, Multiple/physiology , Food Packaging , Glucans/metabolism , Glucans/pharmacology , Humans , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Nisin/pharmacology , Polymers/chemistry , SARS-CoV-2
3.
Molecules ; 27(1)2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1580565

ABSTRACT

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (-36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer-Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.


Subject(s)
Azetidines/pharmacokinetics , Drug Carriers/chemistry , Drug Liberation , Liposomes/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Purines/pharmacokinetics , Pyrazoles/pharmacokinetics , Sulfonamides/pharmacokinetics , Administration, Oral , Animals , Azetidines/administration & dosage , Azetidines/chemistry , Biological Availability , Male , Purines/administration & dosage , Purines/chemistry , Pyrazoles/administration & dosage , Pyrazoles/chemistry , Rats , Rats, Wistar , Sulfonamides/administration & dosage , Sulfonamides/chemistry
4.
Int J Mol Sci ; 22(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572494

ABSTRACT

Low density polyethylene (LDPE) films covered with active coatings containing mixtures of rosemary, raspberry, and pomegranate CO2 extracts were found to be active against selected bacterial strains that may extend the shelf life of food products. The coatings also offer antiviral activity, due to their influence on the activity of Φ6 bacteriophage, selected as a surrogate for SARS-CoV-2 particles. The mixture of these extracts could be incorporated into a polymer matrix to obtain a foil with antibacterial and antiviral properties. The initial goal of this work was to obtain active LDPE films containing a mixture of CO2 extracts of the aforementioned plants, incorporated into an LDPE matrix via an extrusion process. The second aim of this study was to demonstrate the antibacterial properties of the active films against Gram-positive and Gram-negative bacteria, and to determine the antiviral effect of the modified material on Φ6 bacteriophage. In addition, an analysis was made on the influence of the active mixture on the polymer physicochemical features, e.g., mechanical and thermal properties, as well as its color and transparency. The results of this research indicated that the LDPE film containing a mixture of raspberry, rosemary, and pomegranate CO2 extracts incorporated into an LDPE matrix inhibited the growth of Staphylococcus aureus. This film was also found to be active against Bacillus subtilis. This modified film did not inhibit the growth of Escherichia coli and Pseudomonas syringae cells; however, their number decreased significantly. The LDPE active film was also found to be active against Φ6 particles, meaning that the film had antiviral properties. The incorporation of the mixture of CO2 extracts into the polymer matrix affected its mechanical properties. It was observed that parameters describing mechanical properties decreased, although did not affect the transition of LDPE significantly. Additionally, the modified film exhibited barrier properties towards UV radiation. Modified PE/CO2 extracts films could be applied as a functional food packaging material with antibacterial and antiviral properties.


Subject(s)
Food Packaging/methods , Plant Extracts/pharmacology , Polyethylene/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bacteriophage phi 6/drug effects , Biofilms , Chitosan/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Plant Extracts/chemistry , Polyethylene/pharmacology , Polymers/chemistry , Pomegranate , Rosmarinus/chemistry , Rubus , SARS-CoV-2/drug effects
5.
ACS Appl Mater Interfaces ; 13(50): 60612-60624, 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1569206

ABSTRACT

New analytical techniques that overcome major drawbacks of current routinely used viral infection diagnosis methods, i.e., the long analysis time and laboriousness of real-time reverse-transcription polymerase chain reaction (qRT-PCR) and the insufficient sensitivity of "antigen tests", are urgently needed in the context of SARS-CoV-2 and other highly contagious viruses. Here, we report on an antifouling terpolymer-brush biointerface that enables the rapid and sensitive detection of SARS-CoV-2 in untreated clinical samples. The developed biointerface carries a tailored composition of zwitterionic and non-ionic moieties and allows for the significant improvement of antifouling capabilities when postmodified with biorecognition elements and exposed to complex media. When deployed on a surface of piezoelectric sensor and postmodified with human-cell-expressed antibodies specific to the nucleocapsid (N) protein of SARS-CoV-2, it made possible the quantitative analysis of untreated samples by a direct detection assay format without the need of additional amplification steps. Natively occurring N-protein-vRNA complexes, usually disrupted during the sample pre-treatment steps, were detected in the untreated clinical samples. This biosensor design improved the bioassay sensitivity to a clinically relevant limit of detection of 1.3 × 104 PFU/mL within a detection time of only 20 min. The high specificity toward N-protein-vRNA complexes was validated both by mass spectrometry and qRT-PCR. The performance characteristics were confirmed by qRT-PCR through a comparative study using a set of clinical nasopharyngeal swab samples. We further demonstrate the extraordinary fouling resistance of this biointerface through exposure to other commonly used crude biological samples (including blood plasma, oropharyngeal, stool, and nasopharyngeal swabs), measured via both the surface plasmon resonance and piezoelectric measurements, which highlights the potential to serve as a generic platform for a wide range of biosensing applications.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/chemistry , Nasal Mucosa/virology , Polymers/chemistry , RNA, Viral/metabolism , SARS-CoV-2 , Biofouling , Biological Assay , Biosensing Techniques , Humans , Ions , Limit of Detection , Mass Spectrometry , Nasopharynx/virology , Phosphoproteins/chemistry , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Specimen Handling
6.
Sci Rep ; 11(1): 17263, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1550348

ABSTRACT

Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.


Subject(s)
Dexamethasone/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Polymers/chemistry , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/chemistry , Antineoplastic Agents, Hormonal/pharmacokinetics , Child , Dexamethasone/chemistry , Dexamethasone/pharmacokinetics , Drug Liberation , Humans , Kaplan-Meier Estimate , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Treatment Outcome , Tumor Cells, Cultured , Young Adult
7.
Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165

ABSTRACT

BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.


Subject(s)
Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
8.
Chem Commun (Camb) ; 57(80): 10277-10291, 2021 Oct 07.
Article in English | MEDLINE | ID: covidwho-1415963

ABSTRACT

The extensive use of plastic and the absence of efficient and sustainable methods for its degradation has raised critical concerns about its disposal and degradation. Furthermore, the escalated use of personal protective equipment (PPE) and masks during the ongoing COVID-19 pandemic has put us under tremendous pressure of generating huge amounts of plastic waste. Traditional plastic waste disintegration protocols, while effective, pose additional inevitable environmental risks. Owing to this, almost all the used plastic is directly discarded into the marine and terrestrial bodies, causing great harm to the flora and fauna. Plastic has even started entering the food chain in the form of micro- and nano-plastics, leading to deleterious effects. Considering the global need for finding sustainable ways to degrade plastic, several approaches have been developed. Herein we highlight and rationally compare the recent reports on the development of benign alternatives for the sustainable disintegration of plastic detritus into value-added products. Here we discuss, in depth, photoreforming of a variety of polymers to liquid fuels under natural conditions; enzyme-based deconstruction of polymeric materials via microorganisms and their engineered mutants into useful virgin monomers at ambient temperature; and pyrocatalytic degradation of polyethylene through efficient synthetic materials into valuable fuels and waxes. By critically analyzing the methods, we also provide our opinion on such sustainable techniques and discuss newer approaches related to bioinspired and biomimetic chemistry principles for the management of plastic waste.


Subject(s)
Environmental Pollutants/chemistry , Plastics/chemistry , Polymers/chemistry , Sustainable Development , Waste Management/methods , Biodegradation, Environmental , Humans
9.
Molecules ; 26(17)2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1403854

ABSTRACT

This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m2 that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications.


Subject(s)
Polyenes/chemistry , Polymers/chemistry , Biofilms/drug effects , Cell Adhesion/drug effects , Cells, Cultured , Fibroblasts/drug effects , Humans , Materials Testing/methods , Nanofibers/chemistry , Zinc Oxide/chemistry
10.
Bioorg Chem ; 116: 105309, 2021 11.
Article in English | MEDLINE | ID: covidwho-1372894

ABSTRACT

Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.


Subject(s)
Alternaria/chemistry , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Ketones/isolation & purification , Ketones/pharmacology , Polymers/isolation & purification , Polymers/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Humans , Ketones/chemistry , Molecular Structure , Polymers/chemistry
11.
Antiviral Res ; 194: 105162, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347485

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected over 200 million people throughout the world as of August 2021. There are currently no approved treatments providing high chance of recovery from a severe case of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, and the beneficial effect of Remdesivir and passive immunization therapies may only be seen when administered early on disease onset. The emergence of variants is also raising concerns regarding the efficacy of antibody therapies, antivirals, and vaccines. Therefore, there is still a need to develop new antivirals. Here, we investigated the suitability of primary human epithelial cells from the trachea/bronchia (NHBE) and small airway (SAEC) as lung models of SARS-CoV-2 infection to determine, whether the microbicide polyphenylene carboxymethylene (PPCM) has antiviral activity against SARS-CoV-2. Both NHBE and SAEC expressed proteins required for virus entry in lung epithelial cells. However, these cells were only low to moderately permissive to SARS-CoV-2 as titers increased at best by 2.5 log10 during an 8-day kinetic. Levels of replication in SAEC, unlike in NHBE, were consistent with data from other studies using human normal tissues or air-liquid interface cultures, suggesting that SAEC may be more relevant to use than NHBE for drug screening. PPCM EC50 against SARS-CoV-2 was between 32 and 132 µg/ml with a selectivity index between 12 and 41, depending on the cell type and the infective dose used. PPCM doses were consistent with those previously showing effect against other human viruses. Finally, PPCM antiviral effect observed in SAEC was in line with reduction of inflammatory markers observed overly expressed in severe COVID-19 patients. Altogether, our data support the fact that PPCM should be further evaluated in vivo for toxicity and antiviral activity against SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Epithelial Cells/virology , Polymers/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , COVID-19/prevention & control , COVID-19/transmission , Epithelial Cells/drug effects , Humans , Lung/cytology , Lung/virology , Polymers/chemistry , Proof of Concept Study , SARS-CoV-2/genetics , Virus Internalization/drug effects , Virus Replication/drug effects
12.
Sci Adv ; 7(32)2021 08.
Article in English | MEDLINE | ID: covidwho-1343936

ABSTRACT

Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type of "just-right" immune response is critical in the rational design of vaccines for older adults. Here, we report on the mechanism of enhancement of antibody responses by pentablock copolymer micelles, which act as scaffolds for antigen presentation to B cells and cross-link B cell receptors, unlike other micelle-forming synthetic block copolymers. We exploited this unique mechanism and developed these scaffolds as a platform technology to produce antibodies in vitro. We show that this novel approach can be used to generate laboratory-scale quantities of therapeutic antibodies against multiple antigens, including those associated with SARS-CoV-2 and Yersinia pestis, further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases.


Subject(s)
Antibody Formation , Antigen Presentation/immunology , Cross-Linking Reagents/chemistry , Receptors, Antigen, B-Cell/chemistry , Recombinant Fusion Proteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Yersinia pestis/immunology , Adjuvants, Immunologic , Animals , Female , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Polymers/chemistry , Receptors, Antigen, B-Cell/metabolism
13.
Drug Deliv Transl Res ; 11(3): 748-787, 2021 06.
Article in English | MEDLINE | ID: covidwho-1343054

ABSTRACT

The host immune system is highly compromised in case of viral infections and relapses are very common. The capacity of the virus to destroy the host cell by liberating its own DNA or RNA and replicating inside the host cell poses challenges in the development of antiviral therapeutics. In recent years, many new technologies have been explored for diagnosis, prevention, and treatment of viral infections. Nanotechnology has emerged as one of the most promising technologies on account of its ability to deal with viral diseases in an effective manner, addressing the limitations of traditional antiviral medicines. It has not only helped us to overcome problems related to solubility and toxicity of drugs, but also imparted unique properties to drugs, which in turn has increased their potency and selectivity toward viral cells against the host cells. The initial part of the paper focuses on some important proteins of influenza, Ebola, HIV, herpes, Zika, dengue, and corona virus and those of the host cells important for their entry and replication into the host cells. This is followed by different types of nanomaterials which have served as delivery vehicles for the antiviral drugs. It includes various lipid-based, polymer-based, lipid-polymer hybrid-based, carbon-based, inorganic metal-based, surface-modified, and stimuli-sensitive nanomaterials and their application in antiviral therapeutics. The authors also highlight newer promising treatment approaches like nanotraps, nanorobots, nanobubbles, nanofibers, nanodiamonds, nanovaccines, and mathematical modeling for the future. The paper has been updated with the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19.Graphical abstract.


Subject(s)
Antiviral Agents/administration & dosage , Drug Carriers , Nanomedicine , Nanoparticles , Polymers/chemistry , Vaccination , Viral Vaccines/administration & dosage , Virus Diseases/prevention & control , Antiviral Agents/chemistry , COVID-19 Vaccines/administration & dosage , Drug Compounding , Humans , Viral Vaccines/chemistry , Virus Diseases/immunology , Virus Diseases/virology
14.
Molecules ; 26(11)2021 May 31.
Article in English | MEDLINE | ID: covidwho-1323314

ABSTRACT

Dendrimers comprise a specific group of macromolecules, which combine structural properties of both single molecules and long expanded polymers. The three-dimensional form of dendrimers and the extensive possibilities for use of additional substrates for their construction creates a multivalent potential and a wide possibility for medical, diagnostic and environmental purposes. Depending on their composition and structure, dendrimers have been of interest in many fields of science, ranging from chemistry, biotechnology to biochemical applications. These compounds have found wide application from the production of catalysts for their use as antibacterial, antifungal and antiviral agents. Of particular interest are peptide dendrimers as a medium for transport of therapeutic substances: synthetic vaccines against parasites, bacteria and viruses, contrast agents used in MRI, antibodies and genetic material. This review focuses on the description of the current classes of dendrimers, the methodology for their synthesis and briefly drawbacks of their properties and their use as potential therapies against infectious diseases.


Subject(s)
Anti-Infective Agents/pharmacology , Communicable Diseases/drug therapy , Dendrimers/chemistry , Peptides/chemistry , Polymers/chemistry , Animals , Anti-HIV Agents/pharmacology , Bacterial Infections/drug therapy , Biotechnology , COVID-19/drug therapy , Catalysis , Contrast Media , Drug Delivery Systems , Drug Design , HIV Infections/drug therapy , Humans , Infectious Disease Medicine/trends , Magnetic Resonance Imaging , Mice , Nanotechnology , Polypropylenes/chemistry , SARS-CoV-2 , Stereoisomerism , Tomography, X-Ray Computed/trends , Virus Diseases/drug therapy
15.
Int J Mol Sci ; 22(14)2021 Jul 14.
Article in English | MEDLINE | ID: covidwho-1323261

ABSTRACT

Good health, of vital importance in order to carry out our daily routine, consists of both physical and mental health. Tyrosine (Tyr) deficiency as well as its excess are issues that can affect mental health and can generate disorders such as depression, anxiety, or stress. Tyr is the amino acid (AA) responsible for maintaining good mental health, and for this reason, the present research presents the development of new electrochemical sensors modified with polypyrrole (PPy) doped with different doping agents such as potassium hexacyanoferrate (II) (FeCN), sodium nitroprusside (NP), and sodium dodecyl sulfate (SDS) for a selective and sensitive detection of Tyr. The development of the sensors was carried out by chronoamperometry (CA) and the electrochemical characterization was carried out by cyclic voltammetry (CV). The detection limits (LOD) obtained with each modified sensor were 8.2 × 10-8 M in the case of PPy /FeCN-SPCE, 4.3 × 10-7 M in the case of PPy/NP-SPCE, and of 3.51 × 10-7 M in the case of PPy/SDS-SPCE, thus demonstrating a good sensitivity of these sensors detecting L-Tyr. The validation of sensors was carried out through quantification of L-Tyr from three pharmaceutical products by the standard addition method with recoveries in the range 99.92-103.97%. Thus, the sensors present adequate selectivity and can be used in the pharmaceutical and medical fields.


Subject(s)
Carbon/chemistry , Electrodes , Pharmaceutical Preparations/analysis , Pharmaceutical Preparations/chemistry , Polymers/chemistry , Pyrroles/chemistry , Tyrosine/analysis , Electrochemical Techniques
16.
Biosensors (Basel) ; 11(7)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1323109

ABSTRACT

The feasibility of using Superparamagnetic Iron Oxide Nanoparticles (SPIONs) encapsulated by lipid-polymer nanoparticles as labels in lateral flow immunoassays (LFIA) was studied. First, nanoparticles were synthesized with average diameters between 4 and 7 (nm) through precipitation in W/O microemulsion and further encapsulated using lipid-polymer nanoparticles. Systems formulated were characterized in terms of size and shape by DLS (Nanozetasizer from Malvern) and TEM. After encapsulation, the average size was around (≈20 and 50 nm). These controlled size agglomerates were tested as labels with a model system based on the biotin-neutravidin interaction. For this purpose, the encapsulated nanoparticles were conjugated to neutravidin using the carbodiimide chemistry, and the LFIA was carried out with a biotin test line. The encapsulated SPIONs showed that they could be promising candidates as labels in LFIA test. They would be useful for immunomagnetic separations, that could improve the limits of detection by means of preconcentration.


Subject(s)
Immunoassay , Magnetic Iron Oxide Nanoparticles , Biosensing Techniques , Lipids , Polymers/chemistry
17.
Int J Mol Sci ; 22(13)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1304671

ABSTRACT

Hollow vesicles made from a single or double layer of block-copolymer molecules, called polymersomes, represent an important technological platform for new developments in nano-medicine and nano-biotechnology. A central aspect in creating functional polymersomes is their combination with proteins, especially through encapsulation in the inner cavity of the vesicles. When producing polymersomes by techniques such as film rehydration, significant proportions of the proteins used are trapped in the vesicle lumen, resulting in high encapsulation efficiencies. However, because of the difficulty of scaling up, such methods are limited to laboratory experiments and are not suitable for industrial scale production. Recently, we developed a scalable polymersome production process in stirred-tank reactors, but the statistical encapsulation of proteins resulted in fairly low encapsulation efficiencies of around 0.5%. To increase encapsulation in this process, proteins were genetically fused with hydrophobic membrane anchoring peptides. This resulted in encapsulation efficiencies of up to 25.68%. Since proteins are deposited on the outside and inside of the polymer membrane in this process, two methods for the targeted removal of protein domains by proteolysis with tobacco etch virus protease and intein splicing were evaluated. This study demonstrates the proof-of-principle for production of protein-functionalized polymersomes in a scalable process.


Subject(s)
Cell Encapsulation/methods , Nanotechnology/methods , Peptides/chemistry , Polymers/chemistry , Proteins/chemistry , Hydrophobic and Hydrophilic Interactions , Membranes/chemistry
18.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1304665

ABSTRACT

The paper presents a synthesis of poly(l-lactide) with bacteriostatic properties. This polymer was obtained by ring-opening polymerization of the lactide initiated by selected low-toxic zinc complexes, Zn[(acac)(L)H2O], where L represents N-(pyridin-4-ylmethylene) tryptophan or N-(2-pyridin-4-ylethylidene) phenylalanine. These complexes were obtained by reaction of Zn[(acac)2 H2O] and Schiff bases, the products of the condensation of amino acids and 4-pyridinecarboxaldehyde. The composition, structure, and geometry of the synthesized complexes were determined by NMR and FTIR spectroscopy, elemental analysis, and molecular modeling. Both complexes showed the geometry of a distorted trigonal bipyramid. The antibacterial and antifungal activities of both complexes were found to be much stronger than those of the primary Schiff bases. The present study showed a higher efficiency of polymerization when initiated by the obtained zinc complexes than when initiated by the zinc(II) acetylacetonate complex. The synthesized polylactide showed antibacterial properties, especially the product obtained by polymerization initiated by a zinc(II) complex with a ligand based on l-phenylalanine. The polylactide showed a particularly strong antimicrobial effect against Pseudomonas aeruginosa, Staphylococcus aureus, and Aspergillus brasiliensis. At the same time, this polymer does not exhibit fibroblast cytotoxicity.


Subject(s)
Polyesters/chemistry , Polymers/chemistry , Zinc/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Aspergillus/drug effects , Chelating Agents/chemistry , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
19.
J Biol Chem ; 297(2): 100940, 2021 08.
Article in English | MEDLINE | ID: covidwho-1293905

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 envelope protein (S2-E) is a conserved membrane protein that is important for coronavirus (CoV) assembly and budding. Here, we describe the recombinant expression and purification of S2-E in amphipol-class amphipathic polymer solutions, which solubilize and stabilize membrane proteins, but do not disrupt membranes. We found that amphipol delivery of S2-E to preformed planar bilayers results in spontaneous membrane integration and formation of viroporin cation channels. Amphipol delivery of the S2-E protein to human cells results in plasma membrane integration, followed by retrograde trafficking to the trans-Golgi network and accumulation in swollen perinuclear lysosomal-associated membrane protein 1-positive vesicles, likely lysosomes. CoV envelope proteins have previously been proposed to manipulate the luminal pH of the trans-Golgi network, which serves as an accumulation station for progeny CoV particles prior to cellular egress via lysosomes. Delivery of S2-E to cells will enable chemical biological approaches for future studies of severe acute respiratory syndrome coronavirus 2 pathogenesis and possibly even development of "Trojan horse" antiviral therapies. Finally, this work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.


Subject(s)
Cell Membrane/drug effects , Coronavirus Envelope Proteins/metabolism , Polymers/pharmacology , Propylamines/pharmacology , Surface-Active Agents/pharmacology , trans-Golgi Network/metabolism , Cell Membrane/metabolism , Coronavirus Envelope Proteins/genetics , HeLa Cells , Humans , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Lysosomes/metabolism , Polymers/chemistry , Propylamines/chemistry , Protein Transport , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Surface-Active Agents/chemistry
20.
Life Sci ; 280: 119744, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1281492

ABSTRACT

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.


Subject(s)
Nanoparticles/chemistry , Polymers/chemistry , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Vaccination , Viral Vaccines/administration & dosage , Animals , COVID-19/prevention & control , COVID-19/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Drug Carriers/chemistry , Humans , Influenza, Human/prevention & control , Influenza, Human/virology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/virology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Vaccination/methods , Viral Vaccines/therapeutic use
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