ABSTRACT
The development of effective and safe COVID-19 vaccines is a major move forward in our global effort to control the SARS-CoV-2 pandemic. The aims of this study were (1) to develop an inactivated whole-virus SARS-CoV-2 candidate vaccine named BIV1-CovIran and (2) to determine the safety and potency of BIV1-CovIran inactivated vaccine candidate against SARS-CoV-2. Infectious virus was isolated from nasopharyngeal swab specimen and propagated in Vero cells with clear cytopathic effects in a biosafety level-3 facility using the World Health Organization's laboratory biosafety guidance related to COVID-19. After characterisation of viral seed stocks, the virus working seed was scaled-up in Vero cells. After chemical inactivation and purification, it was formulated with alum adjuvant. Finally, different animal species were used to determine the toxicity and immunogenicity of the vaccine candidate. The study showed the safety profile in studied animals including guinea pig, rabbit, mice and monkeys. Immunisation at two different doses (3 or 5 µg per dose) elicited a high level of SARS-CoV-2 specific and neutralising antibodies in mice, rabbits and nonhuman primates. Rhesus macaques were immunised with the two-dose schedule of 5 or 3 µg of the BIV1-CovIran vaccine and showed highly efficient protection against 104 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the BIV1-CovIran vaccine as a potential candidate to induce a strong and potent immune response that may be a promising and feasible vaccine to protect against SARS-CoV-2 infection.
Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccine Potency , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Guinea Pigs , Macaca mulatta , Mice , Rabbits , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vero CellsABSTRACT
The pH-responsive drug release approach in combination with three-dimensional (3D) printing for colon-specific oral drug administration can address the limitations of current treatments such as orally administered solid tablets. Such existing treatments fail to effectively deliver the right drug dosage to the colon. In order to achieve targeted drug release profiles, this work aimed at designing and producing 3D printed tablet shells using Eudragit® FS100 and polylactic acid (PLA) where the core was filled with 100 µl of N-acetylglucosamine (GlcNAc)-loaded methyl cellulose (MC) hydrogel. To meet the requirements of such tablets, the effects of polymer blending ratios and MC concentrations on physical, thermal, and material properties of various components of the tablets and most importantly in vitro drug release kinetics were investigated. The tablets with 80/20 wt% of Eudragit® FS100/PLA and the drug-loaded hydrogel with 30 mg/ml GlcNAc and 3% w/v MC showed the most promising results having the best printability, processability, and drug release kinetics besides being non-cytotoxic. Manufacturing of these tablets will be the first milestone in shifting from the conventional "one size fits all" approach to personalized medicine where different dosages and various combinations of drugs can be effectively delivered to the inflammation site.
Subject(s)
Acetylglucosamine , Methylcellulose , Hydrogels , Tablets , Drug Liberation , Polyesters , Printing, Three-Dimensional , Colon , Hydrogen-Ion Concentration , Technology, Pharmaceutical/methodsABSTRACT
Curcumin is a polyphenolic molecule with antibacterial, antioxidant, anti-inflammatory, and antimicrobial properties. This study aimed to prepare nanocurcumin by encapsulating in biopolymers to improve its stability, bioavailability, water-solubility, antibacterial efficiency against methicillin-resistant Staphylococcus aureus. Three effective variables of curcumin concentration, polymer concentration, and water volume on curcumin-loaded polymer nanoparticles, were optimized. The average size of polyacrylic acid (PAA), polyvinyl alcohol (PVA), and polyethyleneimine (PEI) nanoparticles were obtained 75.2, 77.1, 86.4 nm, respectively. The nanoparticles had a spherical shape, a smooth and uniform surface morphology. The MIC of PAA, PVA, and PEI nanoparticles was 0.480, 0.390, and 0.340 mg/mL, respectively and the MIC of PAA, PVA, and PEI combined with methicillin was 0.330, 0.260, and 0.200 mg/mL, respectively. According to the results, curcumin-loaded PEI nanoparticles had the highest inhibitory effect against methicillin-resistant S. aureus among the synthesized nanoparticles. The results showed that solvent volume, polymer concentration and curcumin concentration had a significant effect on particle size. The inhibitory properties of curcumin nanoparticles significantly increased due to the smaller particle size and increased penetration into the bacterium. Curcumin-loaded nanoparticles can be promising drug carriers for the treatment of infections, cancer, and other diseases.
ABSTRACT
BACKGROUND: In the recent study, optimum operational conditions of cathode compartment of microbial fuel cell were determined by using Response Surface Methodology (RSM) with a central composite design to maximize power density and COD removal. METHODS: The interactive effects of parameters such as, pH, buffer concentration and ionic strength on power density and COD removal were evaluated in two-chamber microbial batch-mode fuel cell. RESULTS: Power density and COD removal for optimal conditions (pH of 6.75, buffer concentration of 0.177 M and ionic strength of cathode chamber of 4.69 mM) improve by 17 and 5%, respectively, in comparison with normal conditions (pH of 7, buffer concentration of 0.1 M and ionic strength of 2.5 mM). CONCLUSIONS: In conclusion, results verify that response surface methodology could successfully determine cathode chamber optimum operational conditions.