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1.
IET Nanobiotechnol ; 16(3): 85-91, 2022 May.
Article in English | MEDLINE | ID: covidwho-1758388

ABSTRACT

Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 µg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.


Subject(s)
Nanoparticles , Silicon Dioxide , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Humans , Nanoparticles/chemistry , Porosity , Silicon Dioxide/chemistry
2.
J Mol Model ; 28(3): 64, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1699453

ABSTRACT

This paper is a summary of research that looks at the potential of fullerene-like (MO)12 nanoclusters (NCs) in drug-carrying systems using density functional theory. Favipiravir/Zn12O12 (- 34.80 kcal/mol), Favipiravir/Mg12O12 (- 34.98 kcal/mol), and Favipiravir/Be12O12 (- 30.22 kcal/mol) were rated in order of drug adsorption degrees. As a result, Favipiravir attachment to (MgO)12 and (ZnO)12 might be simple, increasing Favipiravir loading efficiency. In addition, the quantum theory of atoms in molecules (QTAIM) assessment was utilized to look at the interactions between molecules. The FMO, ESP, NBO, and Eads reactivity patterns were shown to be in excellent agreement with the QTAIM data. The electrostatic properties of the system with the biggest positive charge on the M atom and the largest Eads were shown to be the best. This system was shown to be the best attraction site for nucleophilic agents. The findings show that (MgO)12 and (ZnO)12 have great carrier potential and may be used in medication delivery.


Subject(s)
Amides/administration & dosage , Amides/chemistry , Antiviral Agents/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Pyrazines/administration & dosage , Pyrazines/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Density Functional Theory , Fullerenes/chemistry , Humans , Nanostructures/administration & dosage , Quantum Theory , Spectrophotometry, Ultraviolet , Static Electricity
3.
Int J Mol Sci ; 23(5)2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1699203

ABSTRACT

Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.


Subject(s)
COVID-19/therapy , Drug Delivery Systems/methods , Nanoparticles/administration & dosage , RNA, Small Interfering/administration & dosage , RNAi Therapeutics/methods , Animals , COVID-19/epidemiology , COVID-19/virology , Humans , Models, Genetic , Nanoparticles/chemistry , Pandemics/prevention & control , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics , SARS-CoV-2/physiology
4.
Drug Deliv ; 29(1): 10-17, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1577575

ABSTRACT

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.


Subject(s)
Aerosols , COVID-19 , Drug Delivery Systems , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Nebulizers and Vaporizers , Respiratory Therapy , Aerosols/administration & dosage , Aerosols/adverse effects , COVID-19/prevention & control , COVID-19/transmission , Computer Simulation , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Equipment Design , Humans , Infection Control/methods , Models, Biological , Particle Size , Respiratory Therapy/adverse effects , Respiratory Therapy/instrumentation , Respiratory Therapy/methods , SARS-CoV-2
5.
Int J Biol Macromol ; 198: 101-110, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1587672

ABSTRACT

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Lung Injury/drug therapy , Nanoparticles/chemistry , Silymarin/pharmacology , Administration, Inhalation , Animals , Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , C-Reactive Protein/metabolism , Chamomile/chemistry , Chitosan/chemistry , Chlorocebus aethiops , Curcumin/administration & dosage , Drug Delivery Systems/methods , Flavonoids/analysis , Flavonoids/chemistry , Interleukin-6/metabolism , Lung Injury/blood , Lung Injury/chemically induced , Lung Injury/pathology , Male , Mice , Milk Thistle/chemistry , Nanoparticles/administration & dosage , Oleic Acid/toxicity , Silymarin/administration & dosage , Vero Cells , Viral Plaque Assay
6.
Adv Drug Deliv Rev ; 181: 114081, 2022 02.
Article in English | MEDLINE | ID: covidwho-1568454

ABSTRACT

With numerous recent advances, the field of therapeutic nucleic acid nanotechnology is now poised for clinical translation supported by several examples of FDA-approved nucleic acid nanoformulations including two recent mRNA-based COVID-19 vaccines. Within this rapidly growing field, a new subclass of nucleic acid therapeutics called nucleic acid nanoparticles (NANPs) has emerged in recent years, which offers several unique properties distinguishing it from traditional therapeutic nucleic acids. Key unique aspects of NANPs include their well-defined 3D structure, their tunable multivalent architectures, and their ability to incorporate conditional activations of therapeutic targeting and release functions that enable diagnosis and therapy of cancer, regulation of blood coagulation disorders, as well as the development of novel vaccines, immunotherapies, and gene therapies. However, non-consolidated research developments of this highly interdisciplinary field create crucial barriers that must be overcome in order to impact a broader range of clinical indications. Forming a consortium framework for nucleic acid nanotechnology would prioritize and consolidate translational efforts, offer several unifying solutions to expedite their transition from bench-to-bedside, and potentially decrease the socio-economic burden on patients for a range of conditions. Herein, we review the unique properties of NANPs in the context of therapeutic applications and discuss their associated translational challenges.


Subject(s)
Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nucleic Acids/chemistry , Nucleic Acids/therapeutic use , Animals , COVID-19/drug therapy , COVID-19/immunology , COVID-19 Vaccines/immunology , Drug Delivery Systems/methods , Humans , Immunotherapy/methods , Nanotechnology/methods , SARS-CoV-2/drug effects
7.
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
8.
Cell ; 184(25): 6022-6036.e18, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1536466

ABSTRACT

Viral-deletion mutants that conditionally replicate and inhibit the wild-type virus (i.e., defective interfering particles, DIPs) have long been proposed as single-administration interventions with high genetic barriers to resistance. However, theories predict that robust, therapeutic DIPs (i.e., therapeutic interfering particles, TIPs) must conditionally spread between cells with R0 >1. Here, we report engineering of TIPs that conditionally replicate with SARS-CoV-2, exhibit R0 >1, and inhibit viral replication 10- to 100-fold. Inhibition occurs via competition for viral replication machinery, and a single administration of TIP RNA inhibits SARS-CoV-2 sustainably in continuous cultures. Strikingly, TIPs maintain efficacy against neutralization-resistant variants (e.g., B.1.351). In hamsters, both prophylactic and therapeutic intranasal administration of lipid-nanoparticle TIPs durably suppressed SARS-CoV-2 by 100-fold in the lungs, reduced pro-inflammatory cytokine expression, and prevented severe pulmonary edema. These data provide proof of concept for a class of single-administration antivirals that may circumvent current requirements to continually update medical countermeasures against new variants.


Subject(s)
COVID-19/drug therapy , Virus Replication/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19/metabolism , Cell Line , Chlorocebus aethiops , Culture Media, Conditioned/pharmacology , Drug Delivery Systems/methods , Epithelial Cells , Humans , Male , Mesocricetus , Nanoparticles/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Vero Cells
9.
Acc Chem Res ; 54(23): 4262-4271, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1510542

ABSTRACT

Over the past two decades, research on mRNA-based therapies has exploded, mainly because of the inherent advantages of mRNA, including a low integration probability, transient expression, and simple and rapid in vitro transcription production approaches. In addition, thanks to improved stability and reduced immunogenicity by advanced strategies, the application of mRNA has expanded from protein replacement therapy to vaccination, gene editing and other fields, showing great promise for clinical application. Recently, with the successive launch of two mRNA-based COVID-19 vaccines, mRNA technology has attracted an enormous amount of attention from scientific researchers as well as pharmaceutical companies. Because of the large molecular weight, hydrophilicity, and highly negative charge densities of mRNA, it is difficult to overcome the intracellular delivery barriers. Therefore, various delivery vehicles have been developed to achieve more effective mRNA delivery. In general, conventional mRNA administration methods are based on injection strategies, including intravenous, intramuscular, intradermal, and subcutaneous injections. Although these routes circumvent the absorption barriers to some extent, they bring about injection-related concerns such as safety issues, pain, low compliance, and difficulty in repeated dosing, increasing the need to explore alternative strategies for noninvasive delivery. The ideal noninvasive delivery systems are featured with easy to use, low risks of infection, and good patient compliance. At the same time, they allow patients to self-administer, reducing reliance on professional healthcare workers and interference with bodily functions and daily life. In particular, the noninvasive mucosal delivery of mRNA vaccines can induce mucosal immune responses, which are important for resisting pathogens infected through mucosal routes.Because of the potential clinical benefits mentioned above, we detailed the existing strategies for the noninvasive delivery of mRNA in this review, including delivery via the nasal, pulmonary, vaginal, and transdermal routes. First, we discussed the unique strengths and biological hindrances of each route on the basis of physiology. Next, we comprehensively summarized the research progress reported so far and analyzed the technologies and delivery vehicles used, hoping to provide some references for further explorations. Among these noninvasive routes, nasal and pulmonary delivery are the earliest and most intensively studied areas, mostly owing to their favorable physiological structures: the nasal or pulmonary mucosa is easily accessible, highly permeable and highly vascularized. In contrast, the development of vaginal mRNA delivery is relatively less reported, and the current research mainly focused on some local applications. In addition, microneedles have also been investigated to overcome skin barriers for mRNA delivery in recent years, making microneedle-based delivery an emerging alternative pathway. In summary, a variety of mRNA formulations and delivery strategies have been developed for noninvasive mRNA delivery, skillfully combining appropriate vehicles or physical technologies to enhance effectiveness. We surmise that continuous advances and technological innovations in the development of mRNA noninvasive delivery will accelerate the translation from experimental research to clinical application.


Subject(s)
Drug Delivery Systems/methods , /chemistry , Administration, Cutaneous , Administration, Inhalation , Animals , COVID-19/prevention & control , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification , /immunology
10.
Theranostics ; 11(20): 10012-10029, 2021.
Article in English | MEDLINE | ID: covidwho-1512995

ABSTRACT

Various living organisms have proven to influence human health significantly, either in a commensal or pathogenic manner. Harnessing the creatures may remarkably improve human healthcare and cure the intractable illness that is challenged using traditional drugs or surgical approaches. However, issues including limited biocompatibility, poor biosafety, inconvenience for personal handling, and low patient compliance greatly hinder the biomedical and clinical applications of living organisms when adopting them for disease treatment. Microneedle arrays (MNAs), emerging as a promising candidate of biomedical devices with the functional diversity and minimal invasion, have exhibited great potential in the treatment of a broad spectrum of diseases, which is expected to improve organism-based therapies. In this review, we systemically summarize the technologies employed for the integration of MNAs with specific living organisms including diverse viruses, bacteria, mammal cells and so on. Moreover, their applications such as vaccination, anti-infection, tumor therapy and tissue repairing are well illustrated. Challenges faced by current strategies, and the perspectives of integrating more living organisms, adopting smarter materials, and developing more advanced technologies in MNAs for future personalized and point-of-care medicine, are also discussed. It is believed that the combination of living organisms with functional MNAs would hold great promise in the near future due to the advantages of both biological and artificial species.


Subject(s)
Biological Therapy/methods , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Administration, Cutaneous , Bacteria , Biological Therapy/trends , Cells , Immunotherapy/methods , Immunotherapy/trends , Needles , Skin/drug effects , Vaccination/methods , Vaccination/trends , Viruses
11.
Indian J Pathol Microbiol ; 64(4): 771-775, 2021.
Article in English | MEDLINE | ID: covidwho-1485273

ABSTRACT

CONTEXT: The rapid outbreak of SARS-CoV-2 has become a significant global health concern, highlighting the dire need for antiviral therapeutic agents. RNA-dependent RNA polymerase (RdRp) of coronavirus plays crucial roles in RNA synthesis, and hence remains the druggable target for the treatment of this disease. The most potent broad-spectrum inhibitors of viral RdRp are members of nucleoside analogs (NAs). However, SARS-CoV-2 proved to be a challenging one for the novel NA drug designing strategy because coronavirus possesses an exonuclease (ExoN) domain that is capable of excising NAs, thus showing resistance to existing antiviral drugs. AIM: The objective of our study was to compare the SARS-CoV-2 exonuclease (nsp14) protein sequence of Wuhan-type virus with those of Indian SARS-Cov-2 isolates and to study the effect of multiple mutations on the secondary structure alterations of proteins. SUBJECTS AND METHODS: Multiple-sequence alignment of exonuclease amino-acid sequences followed by phylogenetic analysis and prediction of its secondary structure of the protein was performed. RESULTS: Altogether, seven mutations were detected in the nsp14 of Indian SARS-CoV-2 isolates. Subsequently, prediction of their secondary structures revealed that mutations altered the structural stability of exonuclease proteins. CONCLUSIONS: Present findings, therefore, further suggest that evolvability of SARS-CoV-2 is primarily associated with the onset of multiple novel mutations that rapidly spread at several new locations of the viral genome and also provides important insight to develop specific control strategies to fight against COVID-19 infections.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/genetics , Exonucleases/genetics , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Sequence Analysis, DNA , China , Drug Delivery Systems/methods , Genetic Variation , Genotype , Humans , India , Mutation , Phylogeny
13.
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
14.
Biomed Pharmacother ; 144: 112247, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446461

ABSTRACT

COVID-19 is a pneumonia-like disease with highly transmittable and pathogenic properties caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects both animals and humans. Although many efforts are currently underway to test possible therapies, there is no specific FDA approved drug against SARS-CoV-2 yet. miRNA-directed gene regulation controls the majority of biological processes. In addition, the development and progression of several human diseases are associated with dysregulation of miRNAs. In this regard, it has been shown that changes in miRNAs are linked to severity of COVID-19 especially in patients with respiratory diseases, diabetes, heart failure or kidney problems. Therefore, targeting these small noncoding-RNAs could potentially alleviate complications from COVID-19. Here, we will review the roles and importance of host and RNA virus encoded miRNAs in COVID-19 pathogenicity and immune response. Then, we focus on potential miRNA therapeutics in the patients who are at increased risk for severe disease.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/therapy , Genetic Therapy/methods , MicroRNAs/administration & dosage , Animals , Antiviral Agents/immunology , COVID-19/genetics , COVID-19/immunology , Drug Delivery Systems/methods , Humans , MicroRNAs/genetics , MicroRNAs/immunology
15.
Biomed Pharmacother ; 143: 112162, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401248

ABSTRACT

BACKGROUND: The global healthcare sector has been dealing with a situation known as a novel severe acute respiratory syndrome (SARS-CoV-2) since the end of 2019. Covid-19 is an acronym for Covid-19 (Coronavirus Disease- 2019). It causes a respiratory infection that includes cold, sneezing and coughing, and pneumonia. In the case of an animal, it causes diarrhea and upper respiratory diseases. Covid-19 transmitted human to human via airborne droplets. First Covid-19 emerged in Wuhan market China and it spread rapidly throughout the World. As we know nanoparticles are a novel drug delivery system. They have various advantageous effects like increasing the efficacy of the drug, safety, etc. In this review, we study about the nanoparticles and summarize how it is effective during drug delivery system in Covid-19. Chitosan is a much focused biopolymeric nanoparticle. It delivers drugs to the specific target site. In a recent health crisis, chitosan nanoparticles are one of the ways to release drugs of Covid-19, and specifically in the lungs of the affected patients. We studied and extracted our data from various research papers, review papers, and some other articles. OBJECTIVE: The main goal is to study the nanoparticles and their future aspects which is an effective drug delivery system in Covid-19. METHODS: The bibliographic search was done through a systematic search. The terms "Nanoparticles", "Covid-19 ", "Drug delivery" etc. were used to search the databases/search engines like "Google Scholar", "NCBI", "PubMed", "Science Direct" etc. These databases and search engines used here perform the limited criteria of search to conduct a systematic literature survey for the study and report writing. All the text from the articles and research papers were studied and analyzed. The various articles and research papers were used in writing this report and all of which are mentioned in the reference section of this report. CONCLUSION: Our current studies reveal that nanoparticles may prove very helpful in the delivery of drugs for Covid-19 treatment. Many cases showed that patients, where drugs are delivered with the help of nanoparticles, produced very few side effects.


Subject(s)
COVID-19/drug therapy , Nanoparticles , Animals , Biopolymers/adverse effects , Biopolymers/chemistry , Biopolymers/therapeutic use , COVID-19/virology , Drug Delivery Systems/methods , Humans , Nanomedicine , Nanoparticles/adverse effects , Nanoparticles/chemistry , SARS-CoV-2/pathogenicity
17.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1389404

ABSTRACT

In the past few years, Bruton's tyrosine Kinase (Btk) has emerged as new target in medicinal chemistry. Since approval of ibrutinib in 2013 for treatment of different hematological cancers (as leukemias and lymphomas), two other irreversible Btk inhibitors have been launched on the market. In the attempt to overcome irreversible Btk inhibitor limitations, reversible compounds have been developed and are currently under evaluation. In recent years, many Btk inhibitors have been patented and reported in the literature. In this review, we summarized the (ir)reversible Btk inhibitors recently developed and studied clinical trials and preclinical investigations for malignancies, chronic inflammation conditions and SARS-CoV-2 infection, covering advances in the field of medicinal chemistry. Furthermore, the nanoformulations studied to increase ibrutinib bioavailability are reported.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/administration & dosage , Adenine/administration & dosage , Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/metabolism , COVID-19/drug therapy , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Hematologic Neoplasms/drug therapy , Humans , Inflammation/drug therapy , Neoplasms/drug therapy , Piperidines/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , SARS-CoV-2/drug effects
18.
Int J Mol Sci ; 22(3)2021 Jan 24.
Article in English | MEDLINE | ID: covidwho-1389388

ABSTRACT

The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both viral and bacterial pathogens. The main criterion of vaccine efficacy is the induction of specific humoral and cellular immune responses, and it is well established that immunogenicity depends on the type of vaccine as well as the route of delivery. In addition, antigen delivery to immune organs and the site of injection can potentiate efficacy of the vaccine. In light of this, microvesicles have been suggested as potential vehicles for antigen delivery as they can carry various immunogenic molecules including proteins, nucleic acids and polysaccharides directly to target cells. In this review, we focus on the mechanisms of microvesicle biogenesis and the role of microvesicles in infectious diseases. Further, we discuss the application of microvesicles as a novel and effective vaccine delivery system.


Subject(s)
COVID-19/prevention & control , Extracellular Vesicles/immunology , Immunologic Factors/immunology , SARS-CoV-2/immunology , Viral Vaccines/administration & dosage , Animals , COVID-19/immunology , Drug Delivery Systems/methods , Humans , Vaccination/methods , Viral Vaccines/immunology
19.
Clin Pharmacol Ther ; 108(4): 775-790, 2020 10.
Article in English | MEDLINE | ID: covidwho-1384148

ABSTRACT

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90 ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax ) at an approved dose in humans (Cmax /EC90 ratio). Only 14 of the 56 analyzed drugs achieved a Cmax /EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax /half-maximal effective concentration (EC50 ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Delivery Systems/methods , Drug Repositioning/methods , Pneumonia, Viral/drug therapy , Antiviral Agents/blood , COVID-19 , Coronavirus Infections/blood , Humans , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2
20.
Cell Biol Int ; 45(9): 1807-1831, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1378925

ABSTRACT

Exosomes are nano-sized bioactive vesicles of 30-150 nm in diameter. They are secreted by exocytosis of nearly all type of cells in to the extracellular fluid. Thereby, they can be found in many biological fluids. Exosomes regulate intracellular communication between cells via delivery of their cargo which include lipids, proteins, and nucleic acid. Many desirable features of exosomes made them promising candidates in several therapeutic applications. In this review, we discuss the use of exosomes as diagnostic tools and their possible biomedical applications. Additionally, current techniques used for isolation, purification, and characterization of exosomes from both biological fluids and in vitro cell cultures were discussed.


Subject(s)
Drug Delivery Systems/methods , Exosomes , Cell Communication , Exosomes/chemistry , Exosomes/physiology , Humans
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