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1.
AAPS PharmSciTech ; 23(1): 44, 2021 Dec 29.
Article in English | MEDLINE | ID: covidwho-1595653

ABSTRACT

Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol®, tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients. Graphical Abstract.


Subject(s)
COVID-19 , Curcumin , Antiviral Agents , Feasibility Studies , Humans , Micelles , Molecular Docking Simulation , SARS-CoV-2 , Surface-Active Agents
2.
Molecules ; 26(19)2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1463764

ABSTRACT

Due to their large possibility of the structure modification, alkylammonium gemini surfactants are a rapidly growing class of compounds. They exhibit significant surface, aggregation and antimicrobial properties. Due to the fact that, in order to achieve the desired utility effect, the minimal concentration of compounds are used, they are in line with the principle of greenolution (green evolution) in chemistry. In this study, we present innovative synthesis of the homologous series of gemini surfactants modified at the spacer by the ether group, i.e., 3-oxa-1,5-pentane-bis(N-alkyl-N,N-dimethylammonium bromides). The critical micelle concentrations were determined. The minimal inhibitory concentrations of the synthesized compounds were determined against bacteria Escherichia coli ATCC 10536 and Staphylococcus aureus ATCC 6538; yeast Candida albicans ATCC 10231; and molds Aspergillus niger ATCC 16401 and Penicillium chrysogenum ATCC 60739. We also investigated the relationship between antimicrobial activity and alkyl chain length or the nature of the spacer. The obtained results indicate that the synthesized compounds are effective microbicides with a broad spectrum of biocidal activity.


Subject(s)
Anti-Infective Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Anti-Infective Agents/chemistry , Aspergillus niger/drug effects , Candida albicans/drug effects , Escherichia coli/drug effects , Green Chemistry Technology , Micelles , Microbial Sensitivity Tests , Molecular Structure , Penicillium chrysogenum/drug effects , Quaternary Ammonium Compounds/chemistry , Staphylococcus aureus/drug effects , Surface-Active Agents/chemistry
3.
Eur J Med Chem ; 227: 113910, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1458683

ABSTRACT

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun.


Subject(s)
/chemistry , RNA, Messenger/chemistry , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/chemistry , Humans , Liposomes/chemistry , Micelles , Nanoparticles/chemistry , Peptides/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification
4.
Phytomedicine ; 90: 153651, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1454416

ABSTRACT

BACKGROUND: Although numerous medicinal herbal compounds demonstrate promising therapeutic potential, their clinical application is often limited by their poor oral bioavailability. To circumvent this barrier, various lipid-based herbal formulations have been developed and trialled with promising experimental results. PURPOSE: This scoping review aims to describe the effect of lipid-based formulations on the oral bioavailability of herbal compounds. METHODS: A systematic search was conducted across three electronic databases (Medline, Embase and Cochrane Library) between January 2010 and January 2021 to identify relevant studies. The articles were rigorously screened for eligibility. Data from eligible studies were then extracted and collated for synthesis and descriptive analysis using Covidence. RESULTS: A total of 109 studies were included in the present review: 105 animal studies and four clinical trials. Among the formulations investigated, 50% were emulsions, 34% lipid particulate systems, 12% vesicular systems, and 4% were other types of lipid-based formulations. Within the emulsion system classification, self-emulsifying drug delivery systems were observed to produce the best improvements in oral bioavailability, followed by mixed micellar formulations. The introduction of composite lipid-based formulations and the use of uncommon surfactants such as sodium oleate in emulsion preparation was shown to consistently enhance the bioavailability of herbal compounds with poor oral absorption. Interestingly, the lipid-based formulations of magnesium lithospermate B and Pulsatilla chinensis produced an absolute bioavailability greater than 100% indicating the possibility of prolonged systemic circulation. With respect to chemical conjugation, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was the most frequently used and significantly improved the bioavailability of its phytoconstituents. CONCLUSION: Our findings suggest that there is no distinct lipid-based formulation superior to the other. Bioavailability improvements were largely dependent on the nature of the phytoconstituents. This scoping review, however, provided a detailed summary of the most up-to-date evidence on phytoconstituents formulated into lipid preparations and their oral bioavailability. We conclude that a systematic review and meta-analysis between bioavailability improvements of individual phytoconstituents (such as kaempferol, morin and myricetin) in various lipid-based formulations will provide a more detailed association. Such a review will be highly beneficial for both researchers and herbal manufacturers.


Subject(s)
Biological Availability , Drug Delivery Systems , Micelles , Plant Preparations/pharmacokinetics , Surface-Active Agents , Administration, Oral , Animals , Emulsions , Humans , Lipids , Plant Preparations/administration & dosage , Solubility
5.
J Control Release ; 338: 537-547, 2021 10 10.
Article in English | MEDLINE | ID: covidwho-1385845

ABSTRACT

mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.


Subject(s)
COVID-19 , Micelles , Animals , COVID-19 Vaccines , HeLa Cells , Humans , Mice , Polyethyleneimine , RNA, Messenger , SARS-CoV-2 , Transfection
6.
J Am Chem Soc ; 143(33): 13205-13211, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1349637

ABSTRACT

The receptor binding and proteolysis of Spike of SARS-CoV-2 release its S2 subunit to rearrange and catalyze viral-cell fusion. This deploys the fusion peptide for insertion into the cell membranes targeted. We show that this fusion peptide transforms from intrinsic disorder in solution into a wedge-shaped structure inserted in bilayered micelles, according to chemical shifts, 15N NMR relaxation, and NOEs. The globular fold of three helices contrasts the open, extended forms of this region observed in the electron density of compact prefusion states. In the hydrophobic, narrow end of the wedge, helices 1 and 2 contact the fatty acyl chains of phospholipids, according to NOEs and proximity to a nitroxide spin label deep in the membrane mimic. The polar end of the wedge may engage and displace lipid head groups and bind Ca2+ ions for membrane fusion. Polar helix 3 protrudes from the bilayer where it might be accessible to antibodies.


Subject(s)
Micelles , Peptides/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , COVID-19/pathology , COVID-19/virology , Humans , Hydrophobic and Hydrophilic Interactions , Peptides/chemistry , Phospholipids/chemistry , Phospholipids/metabolism , Protein Binding , Protein Conformation, alpha-Helical , Protein Subunits/chemistry , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/metabolism
7.
Int J Mol Sci ; 22(13)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1299446

ABSTRACT

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.


Subject(s)
Anti-Infective Agents/administration & dosage , Curcumin/administration & dosage , Drug Delivery Systems/methods , Nanoparticles/administration & dosage , Curcumin/chemistry , Humans , Micelles , Nanomedicine/methods , Nanoparticles/chemistry
8.
Eur J Med Chem ; 222: 113584, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1252810

ABSTRACT

Replication of SARS-CoV-2, the coronavirus causing COVID-19, requires a main protease (Mpro) to cleave viral proteins. Consequently, Mpro is a target for antiviral agents. We and others previously demonstrated that GC376, a bisulfite prodrug with efficacy as an anti-coronaviral agent in animals, is an effective inhibitor of Mpro in SARS-CoV-2. Here, we report structure-activity studies of improved GC376 derivatives with nanomolar affinities and therapeutic indices >200. Crystallographic structures of inhibitor-Mpro complexes reveal that an alternative binding pocket in Mpro, S4, accommodates the P3 position. Alternative binding is induced by polar P3 groups or a nearby methyl. NMR and solubility studies with GC376 show that it exists as a mixture of stereoisomers and forms colloids in aqueous media at higher concentrations, a property not previously reported. Replacement of its Na+ counter ion with choline greatly increases solubility. The physical, biochemical, crystallographic, and cellular data reveal new avenues for Mpro inhibitor design.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Cysteine Proteinase Inhibitors/pharmacology , Pyrrolidines/pharmacology , SARS-CoV-2/drug effects , Sulfonic Acids/pharmacology , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Binding Sites , Chlorocebus aethiops , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Crystallography, X-Ray , Cysteine Proteinase Inhibitors/chemical synthesis , Cysteine Proteinase Inhibitors/metabolism , Humans , Micelles , Microbial Sensitivity Tests , Molecular Structure , Protein Binding , Pyrrolidines/chemical synthesis , Pyrrolidines/metabolism , SARS-CoV-2/enzymology , Solubility , Structure-Activity Relationship , Sulfonic Acids/chemical synthesis , Sulfonic Acids/metabolism , Vero Cells
9.
J Biomater Sci Polym Ed ; 32(9): 1219-1249, 2021 06.
Article in English | MEDLINE | ID: covidwho-1160539

ABSTRACT

The recent coronavirus disease-2019 (COVID-19) outbreak has increased at an alarming rate, representing a substantial cause of mortality worldwide. Respiratory injuries are major COVID-19 related complications, leading to poor lung circulation, tissue scarring, and airway obstruction. Despite an in-depth investigation of respiratory injury's molecular pathogenesis, effective treatments have yet to be developed. Moreover, early detection of viral infection is required to halt the disease-related long-term complications, including respiratory injuries. The currently employed detection technique (quantitative real-time polymerase chain reaction or qRT-PCR) failed to meet this need at some point because it is costly, time-consuming, and requires higher expertise and technical skills. Polymer-based nanobiosensing techniques can be employed to overcome these limitations. Polymeric nanomaterials have the potential for clinical applications due to their versatile features like low cytotoxicity, biodegradability, bioavailability, biocompatibility, and specific delivery at the targeted site of action. In recent years, innovative polymeric nanomedicine approaches have been developed to deliver therapeutic agents and support tissue growth for the inflamed organs, including the lung. This review highlights the most recent advances of polymer-based nanomedicine approaches in infectious disease diagnosis and treatments. This paper also focuses on the potential of novel nanomedicine techniques that may prove to be therapeutically efficient in fighting against COVID-19 related respiratory injuries.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Nanomedicine/methods , Nanostructures/therapeutic use , Polymers/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/administration & dosage , Biosensing Techniques , COVID-19/diagnosis , COVID-19/pathology , COVID-19 Testing , COVID-19 Vaccines , Dendrimers , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems , Early Diagnosis , Humans , Lung/pathology , Lung/physiopathology , Micelles , Nanoconjugates/therapeutic use , Nanoparticles , Nanostructures/administration & dosage , Precision Medicine , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/pathology , Tissue Engineering , Treatment Outcome
10.
Int J Mol Sci ; 22(6)2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1125145

ABSTRACT

In order to treat Coronavirus Disease 2019 (COVID-19), we predicted and implemented a drug delivery system (DDS) that can provide stable drug delivery through a computational approach including a clustering algorithm and the Schrödinger software. Six carrier candidates were derived by the proposed method that could find molecules meeting the predefined conditions using the molecular structure and its functional group positional information. Then, just one compound named glycyrrhizin was selected as a candidate for drug delivery through the Schrödinger software. Using glycyrrhizin, nafamostat mesilate (NM), which is known for its efficacy, was converted into micelle nanoparticles (NPs) to improve drug stability and to effectively treat COVID-19. The spherical particle morphology was confirmed by transmission electron microscopy (TEM), and the particle size and stability of 300-400 nm were evaluated by measuring DLSand the zeta potential. The loading of NM was confirmed to be more than 90% efficient using the UV spectrum.


Subject(s)
COVID-19/drug therapy , Computational Biology/methods , Drug Delivery Systems/methods , A549 Cells , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Benzamidines/chemistry , Benzamidines/therapeutic use , Cell Survival/drug effects , Cluster Analysis , Computer Simulation , Databases, Pharmaceutical , Drug Carriers/chemistry , Drug Repositioning , Drug Stability , Glycyrrhizic Acid/chemistry , Glycyrrhizic Acid/therapeutic use , Guanidines/chemistry , Guanidines/therapeutic use , Humans , Hydrophobic and Hydrophilic Interactions , Micelles , Microscopy, Electron, Transmission , Molecular Structure , Nanoparticles/chemistry , Particle Size
11.
J Colloid Interface Sci ; 592: 156-166, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1114489

ABSTRACT

The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV):efavirenz (EFV) anddarunavir (DRV):efavirenz (EFV):ritonavir (RTV),within the core of ß-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission electron microscopy and dynamic light scattering of the ARV-loaded colloidaldispersions indicatefull preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stabilitythe formulations were freeze-driedwithout cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology.Then, theARV-loaded micelles were encapsulated within microparticles of Eudragit® L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditionsin vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations.


Subject(s)
Anti-Retroviral Agents , COVID-19/drug therapy , Caseins , HIV Infections/drug therapy , HIV-1 , Micelles , SARS-CoV-2 , Anti-Retroviral Agents/chemistry , Anti-Retroviral Agents/pharmacokinetics , Anti-Retroviral Agents/pharmacology , Caseins/chemistry , Caseins/pharmacokinetics , Caseins/pharmacology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Drug Combinations , Humans
12.
Trials ; 21(1): 876, 2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-886003

ABSTRACT

OBJECTIVES: To investigates the effectiveness of curcumin-containing Nanomicelles as a therapeutic supplement in the treatment of patients with COVID-19 and its effect on immune responses balance changes following treatment. TRIAL DESIGN: This study is conducted as a prospective, placebo-controlled with parallel group, single-center randomized clinical trial on COVID-19 patients. PARTICIPANTS: Patients are selected from the COVID-19 ward of Shahid Mohammadi Hospital in Bandar Abbas, Iran. INCLUSION CRITERIA: 1. Real time PCR-approved positive COVID-19 test. 2. Both gender 3. Age between 18 and 75 years 4. Signing a written consent 5. Lack of participation in other clinical trials Exclusion criteria: 1. Pregnancy or lactation 2. Allergy to turmeric or curcumin 3. Smoking 4. Patient connected to the ventilator 5. SaO2 less than 90% or PaO2 less than 8 kPa 6. Having comorbidities (such as severe renal failure, Glomerular filtration rate less than 30 ml/min, liver failure, Congestive heart failure, or Chronic obstructive pulmonary disease) 7. History of gallstones 8. History of gastritis or active gastrointestinal ulcer INTERVENTION AND COMPARATOR: In addition to the routine standard treatments for COVID-19, in the intervention group, 40mg nanomicelles containing curcumin (SinaCurcumin Capsule, Exir Nano Sina Company, Iran), four times per day (after breakfast, lunch, dinner and before bedtime) and in the placebo group as the control group, capsules with the same appearance and characteristics (Placebo capsules, Exir Nano Sina Company, Iran) are prescribed for two weeks. MAIN OUTCOMES: The effectiveness of Nano micelles containing curcumin treatment will be evaluated as daily clinical examinations of patients in both groups and, on days 0, 7 and 14, complete clinical symptoms and laboratory findings including peripheral blood and serum parameters such as inflammatory markers will be measured and recorded. Moreover, in order to evaluate the balance of immune responses changes following treatments, serum level of IFN-γ, IL-17, Il-4 and TGF-ß serum cytokines will be measured in both groups at time points of 0, 7 and 14 days post treatment. Gene expression of t-bet, GATA-3, FoxP3 and ROR- γT will also be measured at mentioned time points to assess the shift of T helper1, T helper2, T regulatory and T helper 17 immune responses following treatment. RANDOMISATION: Randomized trials will be performed on 40 COVID-19 patients which will be randomized using encoded sealed boxes with computer generated random digits with 1:1 allocation ratio. In order to randomization, placebo and SinaCurcumin Capsules will be numbered first by computer generated random digits. SinaCurcumin and placebo will then be stored and numbered in sealed packages based on generated random numbers. Finally, according to the order in which patients enter the study, packages are given to patients based on their number. BLINDING (MASKING): The present study will be blind for all patients, physicians and nurses, laboratory technicians and statisticians. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 40 patients will be included in the study, 20 of them will be randomly assigned to the intervention group and 20 to the placebo group. TRIAL STATUS: This is Version 1.0 of protocol dated 21 May 2020. The recruitment was started June 24, 2020 and is expected to be completed by October 31, 2020. TRIAL REGISTRATION: This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20200611047735N1", https://www.irct.ir/trial/48843 . Dated: 19 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus/drug effects , Coloring Agents/therapeutic use , Coronavirus Infections/drug therapy , Curcumin/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/immunology , Biomarkers/metabolism , COVID-19 , Case-Control Studies , Coloring Agents/adverse effects , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Curcumin/adverse effects , Dietary Supplements/adverse effects , Female , Gene Expression/genetics , Humans , Interleukins/immunology , Iran/epidemiology , Male , Micelles , Middle Aged , Pandemics , Placebos/administration & dosage , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Treatment Outcome , Young Adult
13.
Int Immunopharmacol ; 89(Pt B): 107088, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-880513

ABSTRACT

BACKGROUND: As an ongoing worldwide health issue, Coronavirus disease 2019 (COVID-19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients. METHOD: Forty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1ß, IL-6, TNF-α and IL-18 were assessed by Real-time PCR and ELISA, respectively. RESULT: Our primary results indicated that the mRNA expression and cytokine secretion of IL-1ß, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1ß gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin. CONCLUSION: Nano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1ß and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.


Subject(s)
COVID-19/drug therapy , Curcumin/therapeutic use , Cytokines/blood , SARS-CoV-2 , Adult , Aged , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , Cytokines/genetics , Double-Blind Method , Female , Humans , Male , Micelles , Middle Aged , Nanotechnology , RNA, Messenger/analysis , Young Adult
14.
Med Hypotheses ; 143: 110081, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-634173

ABSTRACT

Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19? That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Surface-Active Agents/pharmacology , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/transmission , Humans , Micelles , Models, Biological , Mouthwashes/administration & dosage , Mouthwashes/pharmacology , Pneumonia, Viral/transmission , SARS-CoV-2 , Surface-Active Agents/administration & dosage
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