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1.
World J Microbiol Biotechnol ; 38(12): 230, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2048467

ABSTRACT

Amikacin is an aminoglycoside antibiotic used in drug-resistant bacterial infections. The spread of bacterial infections has become a severe concern for the treatment system because of the simultaneous drug resistance bacteria and SARS-CoV-2 hospitalized patients. One of the most common bacteria in the development of drug resistance is Klebsiella strains, which is a severe threat due to the possibility of biofilm production. In this regard, recent nanotechnology studies have proposed using nanocarriers as a practical proposal to improve the performance of antibiotics and combat drug resistance. Among drug nanocarriers, niosomes are considered for their absorption mechanism, drug coverage, and biocompatibility. In this study, niosomal formulations were synthesized by the thin-layer method. After optimizing the synthesized niosomes, their properties were evaluated in terms of stability and drug release rate. The toxicity of the optimal formulation was then analyzed. The effect of free amikacin and amikacin encapsulated in niosome on biofilm inhibition were compared in multi-drug resistant isolated Klebsiella strains, and the mrkD gene expression was calculated. The MIC and MBC were measured for the free drug and amikacin loaded in the noisome. The particle size of synthesized amikacin-loaded niosomes ranged from 175.2 to 248.3 nm. The results showed that the amount of lipid and the molar ratio of tween 60 to span 60 has a positive effect on particle size, while the molar ratio of surfactant to cholesterol has a negative effect. The highest release rate in amikacin-loaded niosomes is visible in the first 8 h, and then a slower release occurs up to 72 h. The cytotoxicity induced by amikacin-loaded niosome is significantly less than the cytotoxicity of free amikacin in HFF cells (***p < 0.001, **p < 0.01). The mrkD mRNA expression level in the studied strains was significantly reduced after treatment with niosome-containing amikacin compared to free amikacin (***p < 0.001). It was confirmed that in the presence of the niosome, the amikacin antibacterial activity increased while the concentration of the drug used decreased, the formation of biofilm inhibited, and reduced antibiotics resistance in MDR Klebsiella strains.


Subject(s)
Bacterial Infections , COVID-19 , Nanoparticles , Amikacin/pharmacology , Anti-Bacterial Agents/pharmacology , Cholesterol , Humans , Klebsiella pneumoniae , Lipids , Liposomes/pharmacology , Microbial Sensitivity Tests , Polysorbates/pharmacology , RNA, Messenger , SARS-CoV-2 , Surface-Active Agents/pharmacology
2.
Sci Adv ; 8(3): eabj9815, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1634773

ABSTRACT

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , mRNA Vaccines/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/adverse effects , Canada , Cell Line , Cricetinae , Drug Evaluation, Preclinical , Female , HEK293 Cells , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Liposomes/pharmacology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nanoparticles , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/immunology
3.
EBioMedicine ; 74: 103699, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1520831

ABSTRACT

COVID-19 has become a major cause of global mortality and driven massive health and economic disruptions. Mass global vaccination offers the most efficient pathway towards ending the pandemic. The development and deployment of first-generation COVID-19 vaccines, encompassing mRNA or viral vectors, has proceeded at a phenomenal pace. Going forward, nanoparticle-based vaccines which deliver SARS-CoV-2 antigens will play an increasing role in extending or improving vaccination outcomes against COVID-19. At present, over 26 nanoparticle vaccine candidates have advanced into clinical testing, with ∼60 more in pre-clinical development. Here, we discuss the emerging promise of nanotechnology in vaccine design and manufacturing to combat SARS-CoV-2, and highlight opportunities and challenges presented by these novel vaccine platforms.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , Liposomes/pharmacology , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Humans , Nanoparticles , Pandemics/prevention & control , Vaccine Development/methods
4.
Biomed Pharmacother ; 142: 111953, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1322006

ABSTRACT

Currently, there are over 230 different COVID-19 vaccines under development around the world. At least three decades of scientific development in RNA biology, immunology, structural biology, genetic engineering, chemical modification, and nanoparticle technologies allowed the accelerated development of fully synthetic messenger RNA (mRNA)-based vaccines within less than a year since the first report of a SARS-CoV-2 infection. mRNA-based vaccines have been shown to elicit broadly protective immune responses, with the added advantage of being amenable to rapid and flexible manufacturing processes. This review recapitulates current advances in engineering the first two SARS-CoV-2-spike-encoding nucleoside-modified mRNA vaccines, highlighting the strategies followed to potentiate their effectiveness and safety, thus facilitating an agile response to the current COVID-19 pandemic.


Subject(s)
Biomedical Engineering , COVID-19 Vaccines , COVID-19 , Drug Development/methods , Drug Discovery/methods , SARS-CoV-2 , 2019-nCoV Vaccine mRNA-1273 , Biomedical Engineering/methods , Biomedical Engineering/trends , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/classification , COVID-19 Vaccines/pharmacology , Drug Delivery Systems/methods , Humans , Immunogenicity, Vaccine , Liposomes/pharmacology , Nanoparticles , Nucleosides/pharmacology , Nucleosides/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/pharmacology
5.
Nanomedicine ; 35: 102338, 2021 07.
Article in English | MEDLINE | ID: covidwho-921611

ABSTRACT

DNA vaccine is an attractive immune platform for the prevention and treatment of infectious diseases, but existing disadvantages limit its use in preclinical and clinical assays, such as weak immunogenicity and short half-life. Here, we reported a novel liposome-polymer hybrid nanoparticles (pSFV-MEG/LNPs) consisting of a biodegradable core (mPEG-PLGA) and a hydrophilic shell (lecithin/PEG-DSPE-Mal 2000) for delivering a multi-epitope self-replication DNA vaccine (pSFV-MEG). The pSFV-MEG/LNPs with optimal particle size (161.61 ±â€¯15.63 nm) and high encapsulation efficiency (87.60 ±â€¯8.73%) induced a strong humoral (3.22-fold) and cellular immune responses (1.60-fold) compared to PBS. Besides, the humoral and cellular immune responses of pSFV-MEG/LNPs were 1.58- and 1.05-fold than that of pSFV-MEG. All results confirmed that LNPs was a very promising tool to enhance the humoral and cellular immune responses of pSFV-MEG. In addition, the rational design and delivery platform can be used for the development of DNA vaccines for other infectious diseases.


Subject(s)
DNA Replication , Epitopes , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Nanoparticles/therapeutic use , Vaccines, DNA , Animals , Epitopes/genetics , Epitopes/immunology , Liposomes/immunology , Liposomes/pharmacology , Mice , Mice, Inbred BALB C , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vaccines, DNA/pharmacology
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