COVID-19 infection: an overview on cytokine storm and related interventions.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions.

The anti-biofilm activity of hydrogen peroxide against Escherichia coli strain FL-Tbz isolated from a pharmaceutical water system.

Biofilms are considered a significant reason for the failure of disinfection strategies in industrial water systems due to their resistance to antimicrobial agents. This study is designed to investigate the anti-biofilm activity of hydrogen peroxide (H2O2) at combinations of temperatures and contact times. For this purpose, an in vitro microtiter plate (MTP)-based model system was used for biofilm formation using Escherichia coli (E. coli) strain FL-Tbz isolated from the water system of a pharmaceutical plant. To investigate the anti-biofilm activity of H2O2, it was added at different concentrations (2-7% v/v) to biofilms and incubated at different temperatures (20-60 °C) for 10-40 min to find effective conditions to eradicate biofilms. Maximum biofilms were formed when bacterial suspensions were incubated at 37 °C for 96 h. The rate of biofilm formation using an environmental isolate was higher than that of standard strain. H2O2 at concentrations of ≥6.25% (v/v) at temperatures of ≥40 °C incubated for ≥25 min significantly eradicated the biofilms.

Evaluation of the Physicochemical and Biological Stability of Cetuximab under Various Stress Condition.

Cetuximab is a chimeric monoclonal antibody against epidermal growth factor receptor (EGFR) and it is approved for treatment of human colorectal cancer and squamous cell carcinoma of head and neck. The aim of this research was to study the stability of cetuximab finish product (5 mg/mL) under various stress conditions including mechanical, thermal, light stress, and various freeze-thaw cycles. To determine the effects of environmental stresses on the physicochemical properties and bioactivity of cetuximab, a combination of physicochemical and cell-based biological methods including size exclusion chromatography (SEC), cation exchange chromatography (CEX), flow cytometry-based binding assay, and MTS cell viability/proliferation assay was used. The results obtained by the SEC and CEX methods revealed that incubation of cetuximab at 25 and 30 °C, shaking, and various freeze-thaw cycles caused no physicochemical instability. However, functional analysis of the samples exposed to the above-mentioned conditions revealed a significant decrease in the bioactivity of cetuximab indicated by a significant reduction in the cell binding and growth inhibitory effects of cetuximab in EGFR overexpressing cancer cell line (A431). Incubation of cetuximab at 40 and 50 °C led to polymerization and fragmentation of the mAb and resulted in a significant decrease in the bioactivity of the mAb. Our findings show that the light exposure had the most destructive effects on physicochemical and biological characteristics of cetuximab. In conclusion, we found that all mentioned stress conditions significantly affect the bioactivity of cetuximab. Our finding highlights the importance of bioactivity evaluation of biopharmaceuticals in their quality control assessment.

Design and optimization of sustained-release divalproex sodium tablets with response surface methodology.

Response surface methodology is defined as a collection of mathematical and statistical methods that are used to develop, improve, or optimize a product or process. In the present study, a statistical design (Mixture Design) was employed for formulation and optimization of a sustained-release hydrophilic divalproex sodium matrix tablet. Different excipients were used to improve the drug's poor flowability. The hardness of the prepared tablets and also their release pattern were tested. The formulation design was carried out employing mixture design using four excipients in three levels. The Carr's index of formulations and tensile strength were determined and analyzed using Minitab software. The suitable formulations regarding flowability and tablet tensile strength were selected by this software for subsequent drug release studies. The dissolution tests were carried out in acidic and basic phases which were previously proved to be biomimetic. Samples were analyzed using HPLC, and release data were compared to Depakine® (sustained-release divalproex from Sanofi). Release kinetics was also determined for selected formulations. Selected formulations were subjected to dissolution test and showed similar dissolution profiles with Depakine® based on difference and similarity factor calculations. The software selected an optimized formulation which had a slightly different release pattern in vitro compared to innovator but of nearly zero-order kinetics. It can be concluded that application of Mixture Design is a shortcut method to design suitable formulations of sustained-release divalproex sodium containing hydrophilic matrix tablets by direct compression method.

Nanoparticle and Stem Cell Combination Therapy for the Management of Stroke.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

Nanoparticle-based delivery platforms for the enhanced oral delivery of peptides/proteins.

Biopharmaceutical products are currently well-established in nearly all branches of medicine and are believed to have great potential for the treatment of a broad spectrum of diseases. Peptide/protein drugs exhibit a predominant class of new biopharmaceuticals coming on the market in recent years. Oral delivery of peptides/proteins as a non-invasive therapeutic technique has become an appealing alternative to the parenteral route. However, the efficient oral delivery of peptides/proteins is limited because of their high molecular weight, poor stability and low biodistribution. Nanoparticles (NPs) have shown excellent results in peptide/protein delivery research. In this paper, the use of NPs as delivery systems for peptides/proteins and their ability to be efficiently delivered via the oral route have been described.

Medicines made from peptides and proteins have become important for treating various diseases. One challenge is delivering them effectively through the mouth, as they can be fragile and may not distribute well in the body. Scientists have been studying the use of tiny particles called nanoparticles (NPs) to help solve these problems. In this article, we explore how NPs can enhance the delivery of peptide/protein medicines when taken orally. By using NPs as delivery platforms, these medicines can be protected and absorbed more efficiently, leading to better treatment outcomes.

Nanoparticle Formulations of Antioxidants for the Management of Oxidative Stress in Stroke: A Review.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, there has been a lack of effective stroke treatment. Therefore, novel treatment strategies are needed to decrease stroke-induced morbidity and promote the patient's quality of life. Reactive oxygen species (ROS) have been recognized as one of the major causes of brain injury after ischemic stroke. Antioxidant therapy seems to be an effective treatment in the management of oxidative stress relevant to inflammatory disorders like stroke. However, the in vivo efficacy of traditional anti-oxidative substances is greatly limited due to their non-specific distribution and poor localization in the disease region. In recent years, antioxidant nanoparticles (NPs) have demonstrated a clinical breakthrough for stroke treatment. Some NPs have intrinsic antioxidant properties and act as antioxidants to scavenge ROS. Moreover, NPs provide protection to the antioxidant agents/enzymes while effectively delivering them into unreachable areas like the brain. Because of their nanoscale dimensions, NPs are able to efficiently pass through the BBB, and easily reach the damaged site. Here, we discuss the challenges, recent advances, and perspectives of antioxidant NPs in stroke treatment.

Taurine in Septic Critically Ill Patients: Plasma versus Blood.

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.

Modulation of the Immune System Mechanisms using Probiotic Bacteria in Allergic Diseases: Focus on Allergic Retinitis and Food Allergies.

Allergic illnesses occur when an organism's immune system is excessively responsive to certain antigens, such as those that are presented in the environment. Some people suffer from a wide range of immune system-related illnesses including allergic rhinitis, asthma, food allergies, hay fever, and even anaphylaxis. Immunotherapy and medications are frequently used to treat allergic disorders. The use of probiotics in bacteriotherapy has lately gained interest. Probiotics are essential to human health by modulating the gut microbiota in some ways. Due to probiotics' immunomodulatory properties present in the gut microbiota of all animals, including humans, these bacterial strains can prevent a wide variety of allergic disorders. Probiotic treatment helps allergy patients by decreasing inflammatory cytokines and enhancing intestinal permeability, which is important in the battle against allergy. By altering the balance of Th1 and Th2 immune responses in the intestinal mucosa, probiotics can heal allergic disorders. Numerous studies have shown a correlation between probiotics and a reduced risk of allergy disorders. A wide range of allergic disorders, including atopic dermatitis, asthma, allergic retinitis and food allergies has been proven to benefit from probiotic bacteria. Therefore, the use of probiotics in the treatment of allergic diseases offers a promising perspective. Considering that probiotic intervention in the treatment of diseases is a relatively new field of study, more studies in this regard seem necessary.

Development and characterization of a novel mucoadhesive sol-gel suppository of sumatriptan: design, optimization, in vitro and ex vivo evaluation for rectal drug delivery.

Aim: Sumatriptan (ST) is used for the treatment of migraine and cluster headaches. However, it exhibits low oral bioavailability (15%) due to the high first-pass metabolism. The aim of this work was to formulate an ST rectal hydrogel. Methods: Hydrogels were formulated according to a Box-Behnken design using pluronic F-127 (PF-127) and chitosan as thermogelling and mucoadhesive agents, respectively. The rectal permeability was examined using a sheep rectal mucosa. Results: Among all the formulations, the hydrogel S2 showed satisfactory drug content (4.50%), gelling temperature (32°C), pH (6.41), viscosity (105 cP) and strength (15.90 sec). Mucoadhesive strength was adequate to provide a prolonged residence time. The flux of hydrogel S2 was calculated to be 0.0003 µg/cm2.min. Conclusion: The ST hydrogel can provide a potential opportunity to overcome the first pass metabolism and reduce drug dose.

The Therapeutic Benefits of Intravenously Administrated Nanoparticles in Stroke and Age-related Neurodegenerative Diseases.

The mean global lifetime risk of neurological disorders such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) has shown a large effect on economy and society. Researchers are still struggling to find effective drugs to treat neurological disorders and drug delivery through the blood-brain barrier (BBB) is a major challenge to be overcome. The BBB is a specialized multicellular barrier between peripheral blood circulation and neural tissue. Unique and selective features of the BBB allow it to tightly control brain homeostasis as well as the movement of ions and molecules. Failure in maintaining any of these substances causes BBB breakdown and subsequently enhances neuroinflammation and neurodegeneration. BBB disruption is evident in many neurological conditions. Nevertheless, the majority of currently available therapies have tremendous problems with drug delivery into the impaired brain. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem. NPs are colloidal systems with a size range of 1-1000 nm which can encapsulate therapeutic payloads, improve drug passage across the BBB, and target specific brain areas in neurodegenerative/ischemic diseases. A wide variety of NPs has been displayed for the efficient brain delivery of therapeutics via intravenous administration, especially when their surfaces are coated with targeting moieties. Here, we discuss recent advances in the development of NP-based therapeutics for the treatment of stroke, PD, and AD, as well as the factors affecting their efficacy after systemic administration.

Application of Nano-based Drug Loading Systems in the Treatment of Neurological Infections: An Updated Review.

Infection of the central nervous system (CNS) is a global healthcare concern with high rates of death and disease. CNS infections mainly include meningitis, encephalitis, and brain abscesses. Bacteria, viruses, fungi, protozoa, and parasites are the most common causes of neuroinfections. There are many types of medications used in the treatment of CNS infections, but drug delivery through the blood-brain barrier (BBB) is a major challenge to overcome. The BBB is a specialized multicellular barrier separating the neural tissue from the peripheral blood circulation. Unique characteristics of the BBB allow it to tightly control the movement of ions and molecules. Thus, there is a critical need to deal with these conditions with the aim of improving novel antimicrobial agents. Researchers are still struggling to find effective drugs to treat CNS infections. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem because NPs can be tailored to facilitate drug transport across the BBB. NPs are colloidal systems with a size range of 1-1000 nm, which can be used to encapsulate therapeutics, improve drug transport across the BBB, and target specific brain areas in CNS infections. A wide variety of NPs has been displayed for the CNS delivery of therapeutics, especially when their surfaces are coated with targeting moieties. This study aimed to review the available literature on the application of NPs in CNS infections.

The Factors Determining the Skin Penetration and Cellular Uptake of Nanocarriers: New Hope for Clinical Development.

The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly difficult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in skin penetration of nanocarriers containing the drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use to avoid possible toxic effects. Nanocarriers can act as a means to increase skin permeation of drugs by supporting direct interaction with the SC and increasing the period of permanence on the skin. Skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry, as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.

Safety and Toxicity Issues of Therapeutically Used Nanoparticles from the Oral Route.

The emerging science of nanotechnology sparked a research attention in its potential benefits in comparison to the conventional materials used. Oral products prepared via nanoparticles (NPs) have garnered great interest worldwide. They are used commonly to incorporate nutrients and provide antimicrobial activity. Formulation into NPs can offer opportunities for targeted drug delivery, improve drug stability in the harsh environment of the gastrointestinal (GI) tract, increase drug solubility and bioavailability, and provide sustained release in the GI tract. However, some issues like the management of toxicity and safe handling of NPs are still debated and should be well concerned before their application in oral preparations. This article will help the reader to understand safety issues of NPs in oral drug delivery and provides some recommendations to the use of NPs in the drug industry.

Nanoparticles for antimicrobial purposes in Endodontics: A systematic review of in vitro studies.

INTRODUCTION: Antimicrobial nanoparticles with enhanced physiochemical properties have attracted attention as modern antimicrobials, especially in the complicated oral cavity environment. The goal of the present article is to review the current state of nanoparticles used for antimicrobial purposes in root canal infections. METHODS: A review was conducted in electronic databases using MeSH keywords to identify relevant published literature in English. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA-guidelines). No restrictions on publication date were imposed. Data regarding root canal disinfections, general antimicrobial mechanisms of nanoparticles, type of nanoparticles as antimicrobial agent and antimicrobial effect of nanoparticles in endodontics were collected and subjected to descriptive data analysis. RESULTS: The literature search in electronic databases according to the inclusion criteria provided 83 titles and abstracts. Among them 15 papers were related to antimicrobial effect of nanoparticles in Endodontics. Silver nanoparticles with sustainable activity were the most studied agent for its antimicrobial behavior in root canal infection. Aided polymeric nanoparticles with photo or ultrasound, glass bioactive nanoparticles as well as Calcium derivative based nanoparticles, with improved activity in comparison with the non-nano counterparts, are of importance in infection control of dental root canal. Bioactive Non-organic nanoparticles with structural capabilities present enhanced antimicrobial activity in root canal infections. DISCUSSION: All included studies showed an enhanced or at least equal effect of nanoparticulate systems to combat dental root canal infections compared to conventional antimicrobial procedures. However, it is crucial to understand their shortcomings and their probable cellular effects and toxicity as well as environmental effects.