Increased Efficiency of Radiation Inactivation of Virions by Gold Nanoparticles

Gold nanoparticles (GNPs) are promising radiosensitizers for cancer radiotherapy. Moreover, they can be used in the same way for radiation processing and sterilization. Such application of GNPs is of practical interest since it may significantly reduce the dose load and expand the application of radiation treatment. In the present study, the high radiosensitization effect of GNPs in relation to viral particles is demonstrated for the first time. The preparations of tobacco mosaic virus (TMV) are used as an experimental model, insofar as this virus has the same properties as animal and human ones but is safe for humans. Irradiation with 45 kVp X-ray to the doses of 4 and 7 kGy leads to a decrease in the infectious activity of TMV virions up to 1.92- and 2.70-fold, respectively. At the same time, irradiation in the presence of 0.4 mg mL(-1) of 12 nm spherical GNPs increases the efficiency of virus inactivation up to 15- and 22-fold. The GNPs enhance both the damage to capsid protein due to the enhanced generation of reactive oxygen species and genome RNA due to the emission of secondary radiation. These results show the great prospects of the application of high-Z nanoparticles in radiation treatment.

Process Development and Manufacturing: EXPANSION OF DIFFERENT TYPES OF THERAPEUTIC CELLS USING XENOGENEIC FREE AND GAMMA IRRADIATED HUMAN PLATELET LYSATE

Background & Aim: Mill Creek’s human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food & Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. However, over the past few decades, the number of emerging infectious diseases that spread to people has increased. Even though transmission of Covid-19 and other potential emergent pathogens via blood transfusion has not been documented, adventitious agents remain a concern. For that reason, pathogen reduction processes are necessary to improve the safety profile of blood-derived products used in the manufacture of cellbased therapies. One of these processes is the pathogen reduction through gamma irradiation. Methods, Results & Conclusion: Previously, we validated a process to produce gamma irradiated human platelet lysate. To be able to release the gamma irradiated product as a pathogen reduced product, we additionally performed a viral clearance study, which determined the efficacy of the process to actually reduce a potential viral contaminant. Here, we present the results obtained from the viral clearance study performed on our gamma irradiated hPL, and from the expansion of different types of therapeutic cells using our gamma irradiated hPLs, which showed unprecedented levels of product quality and efficiency. Our products are a game changer for the growing market of cell base therapies bioprocessing and manufacturing.

Methods of Inactivation of Highly Pathogenic Viruses for Molecular, Serology or Vaccine Development Purposes.

The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the Togaviridae, Flaviviridae, Filoviridae, Arenaviridae, Hantaviridae, Peribunyaviridae, Phenuiviridae, Nairoviridae and Orthomyxoviridae families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here.

Aspects of the physiochemical properties of SARS-CoV-2 to prevent S-protein receptor binding using Arabic gum

With the number of people infected with the new coronavirus exceeding millions of confirmed infections, the world is turning to scientists and researchers, everyone is waiting - impatiently - for the results of the research that is being carried out in full swing to find an effective treatment for the virus. The recent development of the virus has witnessed at least 17 mutations that may affect its external shape, especially on the S-protein receptor-binding domain (RBD), which helps it attach to human cells' receptor angiotensin-converting enzyme-2 (ACE2) to make RBD-ACE2 interaction and entry to host cell. This interaction becomes stronger in the new strains of the coronavirus due to a mutation that occurs in the S-proteins that attach to human cells. For researchers and scientists to be able to confront this pandemic that has spread in the world like wildfire, they must be armed with accurate understanding and clear knowledge about coronavirus. This study focuses on polysaccharides, specifically negatively polysaccharides, that can interfere with the positive charge of the surface of the SARS-CoV-2 and ACE2, thus inhibiting the virus's infectivity and destroying it. In addition, polysaccharides will boost the immune function of the vaccine, thereby fostering nonspecific immunity of the body and specific immunity of the body, cellular immunity, mucosal immunity, humoral immunity, and decreased pro-inflammatory expression. This research aims to reduce the attachment power and modify the pulling apart of the RBD and the angiotensin-converting enzyme 2 (ACE2) by polysaccharide molecules such as Arabic gum (AG) and carrageenan. The adapted fluorometric assay is used to investigate the probability of Arabic gum and ACE2 interactions. The obtained results confirmed that the interaction could take place between Arabic gum and ACE2. Several literature studies promote the use of the urchin egg as antiviral, especially for SARS-CoV-2, because it has sulfated fucan polysaccharide molecules that prevent interaction of SARS-CoV-2 with a host cell. But, to the best of our knowledge, we found that the effect of urchin egg as antiviral, especially for SARS-CoV-2 is very difficult due to the presence of immunoglobulin G (IgG) in the human cells containing sugars that terminate with N-glycolylneuraminic (Neu5Ac) as found in the sperm of sea urchin. So, s most probably an interaction has occurred between Neu5Ac in IgG of human cells and sulfated fucan polysaccharide molecules of urchin egg.

Effects of the 3DP process parameters on mechanical properties of polylactic acid part used for medical purposes

PurposeThis paper aims to investigate effect of infill density, fabricated built orientation and dose of gamma radiation to mechanical tensile and compressive properties of polylactic acid (PLA) part fabricated by fused deposit modelling (FDM) technique for medical applications.Design/methodology/approachPLA specimens for tensile and compressive tests were fabricated using FDM machine. The specimens geometry and test method were referred to ASTM D638 and ASTM D695, respectively. Three orientations under consideration were flat, edge and upright, whereas the infill density ranged from 0 to 100%. The gamma radiation dose used to expose to specimens was 25 kGy. The collected data included stress and strain, which was used to find mechanical properties, i.e. yield strength, ultimate tensile strength (UTS), fracture strength, elongation at yield, elongation at UTS and elongation at break. The t-test was used to access the difference in mechanical properties.FindingsCompressive mechanical properties is greater than tensile mechanical properties. Increasing number of layer parallel to loading direction and infill density, it enhances the material property. Upright presents the lowest mechanical property in tensile test, but greatest in compressive test. Upright orientation should not be used for part subjecting to tensile load. FDM is more proper for part subjecting to compressive load. FDM part requires undergoing gamma ray for sterilisation, the infill density no less than 70 and 60% should be selected for part subjecting to tensile and compressive load, respectively.Originality/valueThis study investigated all mechanical properties in both tension and compression as well as exposure to gamma radiation. The results can be applied in selection of FDM parameters for medical device manufacturing.

How to Sterilize Polylactic Acid Based Medical Devices?

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented.

Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development.

Radiation inactivation of enveloped viruses occurs as the result of damages at the molecular level of their genome. The rapidly emerging and ongoing coronavirus disease 2019 (COVID-19) pneumonia pandemic prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global health crisis and an economic devastation. The readiness of an active and safe vaccine against the COVID-19 has become a race against time in this unqualified global panic caused by this pandemic. In this review, which we hope will be helpful in the current situation of COVID-19, we analyze the potential use of γ-irradiation to inactivate this virus by damaging at the molecular level its genetic material. This inactivation is a vital step towards the design and development of an urgently needed, effective vaccine against this disease.

Biochemical study on the protective effect of curcumin on acetaminophen and gamma-irradiation induced hepatic toxicity in rats.

Acetaminophen (APAP) is one of the few recommended analgesic and antipyretic drugs in some critical cases such as viral disease COVID-19. However, the unrestricted use of APAP develops liver disorders. Hepatotoxicity and liver injury can also be induced by ionizing radiation (IR) during radiotherapy. The data of the current study represents that treatment of rats with either APAP-overdose, or gamma-irradiation (R) induces hepatotoxicity, results in significant increases of the hepatic-enzymes activities (ALT, AST, ALP, GGT, LDH, and MDH), as well as enhancement of triglycerides, total cholesterol levels, combined with declines in albumin and total protein contents. An enhancement of the lipid peroxides (malondialdehyde; MDA), and nitric oxide levels along with a decline of reduced glutathione contents and suppression of superoxide dismutase, catalase, and glutathione peroxidase activities are also observed within the liver tissues of intoxicated animals. TNF-α, IL-1ß, IL-6, iNOS, Cytochrome P450 2E1 (CYP2E1), miR-802 gene expression, NF-κB, and calcium levels are up-regulated, while Nuclear factor erythroid-related factor-2 (Nrf2), Hemoxygenase-1 (HO-1) protein and gene expressions, as well as, glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H-Quinone oxidoreductase (NQO1), and miR-122 gene expressions are down-regulated in the livers of intoxicated animals. All these parameters show significant improvement in R/APAP intoxicated animals. Curcumin pretreatment develops an amelioration of these effects in APAP-overdose, R-exposure, or R/APAP treatments. In conclusion, oral administration of curcumin shows hepatoprotective effects against APAP-overdose induced hepatic damage in normal and gamma-irradiated rats through prospective regulation of the therapeutic targets CYP2E1, Nrf2, and NF-κB, via organizing the miR-122 and miR-802 gene expression.

Sterilization of N95 respirators: The time for action is upon us!

Re-processing of primary protective equipment is the need of the hour with healthcare systems all over the world strained due to the shortage precipitated by severe acute respiratory syndrome coronavirus 2. The common methods of re-sterilization do not hold well for filtering facepiece respirators (FFRs) as they affect their structure and function. We propose the validation and eventual use of gamma irradiation, an already existing method of re-sterilization, to disinfect FFRs in bulk.