Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Int J Mol Sci ; 22(23)2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1559503

ABSTRACT

Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug's toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80-200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).


Subject(s)
Amino Acids/chemistry , Drug Carriers/administration & dosage , Drug Carriers/chemical synthesis , Fluorouracil/pharmacology , Mammary Neoplasms, Experimental/drug therapy , Nanoparticles/administration & dosage , Animals , Antimetabolites, Antineoplastic/chemistry , Antimetabolites, Antineoplastic/pharmacology , Female , Fluorouracil/chemistry , Mammary Neoplasms, Experimental/pathology , Nanoparticles/chemistry , Tumor Cells, Cultured
2.
Chem Biol Interact ; 351: 109706, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1464614

ABSTRACT

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.


Subject(s)
Drug Carriers/chemistry , Lung/metabolism , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Lung/drug effects , Lung Diseases/drug therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptides/therapeutic use , Proteins/therapeutic use
3.
Cancer Treat Res Commun ; 28: 100425, 2021.
Article in English | MEDLINE | ID: covidwho-1281406

ABSTRACT

BACKGROUND: Malignancy is one of the prime global causes of mortality. Cancer Patients suffering from SARS-CoV-2 have demonstrated higher rates of severe complications exacerbating towards death. Possible genetic and epigenetic alterations may exist in cancer patients which have the potential to contribute towards their increased vulnerability towards COVID-19. METHOD: An exhaustive literature search using 'COVID-19', 'SARS-CoV-2', 'Cancer', 'Malignancy', 'Relationships', Interlinks', 'Genetic', 'Epigenetic', 'Epidemiological studies', 'Clinical Studies', 'Vaccination', 'Vaccine scenario' were conducted in PubMed and EMBASE till 2nd June 2021. RESULT: In this narrative review, 17 epidemiological studies were listed which focused on clinical parameters of several malignancy patient cohorts who contracted COVID-19. Besides, genetic and epigenetic alterations seen among cancer patients are also discussed which may plausibly increase the vulnerability of cancer patients to SARS-CoV-2 infection. Also, global vaccination scenario among malignant patients along with the necessity to prioritize them in the vaccination campaigns are also elaborated. CONCLUSION: Genetic and epigenetic modifications present in ACE2, TMPRSS2, IL-6 and several cytokines require more in-depth research to elucidate the shared mechanisms of malignancy and SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/genetics , Neoplasms/genetics , Angiotensin-Converting Enzyme 2/genetics , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Clinical Trials as Topic , Drug Carriers/administration & dosage , Epigenesis, Genetic , Genetic Predisposition to Disease , Humans , Interleukin-6/genetics , Neoplasms/epidemiology , Neoplasms/immunology , Vaccination
4.
J Mater Chem B ; 9(35): 6988-6993, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1262017

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Carriers/chemistry , Nanoparticles/chemistry , Pulmonary Surfactants/therapeutic use , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Injections, Intravenous , Lung , Nanoparticles/administration & dosage , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/chemistry , SARS-CoV-2
5.
Sci Rep ; 11(1): 371, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1242035

ABSTRACT

Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.


Subject(s)
Horses , Nasal Sprays , RNA, Messenger/administration & dosage , Respiratory Mucosa , Animals , Animals, Newborn , Cells, Cultured , Drug Carriers/administration & dosage , Drug Carriers/adverse effects , Drug Carriers/pharmacokinetics , Drug Delivery Systems/adverse effects , Drug Delivery Systems/methods , Drug Delivery Systems/veterinary , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/drug effects , Lung/metabolism , Nebulizers and Vaporizers/veterinary , Polyethyleneimine/administration & dosage , Polyethyleneimine/chemistry , RNA, Messenger/adverse effects , RNA, Messenger/pharmacokinetics , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Transcription, Genetic , Transfection/methods , Transfection/veterinary , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects , Vaccines, DNA/pharmacokinetics
6.
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
7.
Adv Drug Deliv Rev ; 171: 215-239, 2021 04.
Article in English | MEDLINE | ID: covidwho-1014284

ABSTRACT

The SARS-CoV-2 global pandemic has seen rapid spread, disease morbidities and death associated with substantive social, economic and societal impacts. Treatments rely on re-purposed antivirals and immune modulatory agents focusing on attenuating the acute respiratory distress syndrome. No curative therapies exist. Vaccines remain the best hope for disease control and the principal global effort to end the pandemic. Herein, we summarize those developments with a focus on the role played by nanocarrier delivery.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Drug Carriers/administration & dosage , Nanocapsules/administration & dosage , SARS-CoV-2/drug effects , Animals , COVID-19/immunology , COVID-19 Vaccines/immunology , Drug Delivery Systems/methods , Drug Delivery Systems/trends , Humans , SARS-CoV-2/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
8.
Molecules ; 25(11)2020 Jun 11.
Article in English | MEDLINE | ID: covidwho-981163

ABSTRACT

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus OC43, Human/drug effects , Flavonoids/pharmacology , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/chemistry , Betacoronavirus/chemistry , Betacoronavirus/growth & development , Binding Sites , COVID-19 , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus Infections/genetics , Coronavirus OC43, Human/chemistry , Coronavirus OC43, Human/growth & development , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Flavonoids/chemistry , Humans , Interleukins/antagonists & inhibitors , Interleukins/chemistry , Interleukins/genetics , Interleukins/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/virology , Lung/drug effects , Lung/pathology , Lung/virology , Mice , Molecular Docking Simulation , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phytotherapy/methods , Pneumonia, Viral/genetics , Primary Cell Culture , Protein Binding , Protein Interaction Domains and Motifs , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Virus Internalization/drug effects
9.
Biomaterials ; 267: 120389, 2021 01.
Article in English | MEDLINE | ID: covidwho-898508

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/drug therapy , DNA/blood , Deoxyribonuclease I/therapeutic use , Drug Carriers/administration & dosage , Nanoparticles/administration & dosage , Neutrophils/drug effects , SARS-CoV-2 , Sepsis/drug therapy , Animals , COVID-19/blood , COVID-19/immunology , Cytokine Release Syndrome/etiology , Deoxyribonuclease I/administration & dosage , Dexamethasone/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Extracellular Traps/drug effects , Humans , Indoles , Male , Mice , Mice, Inbred C57BL , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , NF-kappa B/blood , Neutrophils/enzymology , Peroxidase/blood , Polyethylene Glycols , Polyglactin 910 , Polymers , Sepsis/etiology , Sepsis/immunology
10.
J Control Release ; 328: 776-791, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-753326

ABSTRACT

Over the past decade, the growing interest in targeted lung cancer therapy has guided researchers toward the cutting edge of controlled drug delivery, particularly magnetic particle targeting. Targeting of tissues by magnetic particles has tackled several limitations of traditional drug delivery methods for both cancer detection (e.g., using magnetic resonance imaging) and therapy. Delivery of magnetic particles offers the key advantage of high efficiency in the local deposition of drugs in the target tissue with the least harmful effect on other healthy tissues. This review first overviews clinical aspects of lung morphology and pathogenesis as well as clinical features of lung cancer. It is followed by reviewing the advances in using magnetic particles for diagnosis and therapy of lung cancers: (i) a combination of magnetic particle targeting with MRI imaging for diagnosis and screening of lung cancers, (ii) magnetic drug targeting (MDT) through either intravenous injection and pulmonary delivery for lung cancer therapy, and (iii) computational simulations that models new and effective approaches for magnetic particle drug delivery to the lung, all supporting improved lung cancer treatment. The review further discusses future opportunities to improve the clinical performance of MDT for diagnosis and treatment of lung cancer and highlights clinical therapy application of the MDT as a new horizon to cure with minimal side effects a wide variety of lung diseases and possibly other acute respiratory syndromes (COVID-19, MERS, and SARS).


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems/methods , Lung Neoplasms , Magnets/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/therapeutic use , Drug Carriers/administration & dosage , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Magnetic Resonance Imaging , Molecular Targeted Therapy , Nanoparticles/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL