Inflammation and Mental Health Disorders: Immunomodulation as a Potential Therapy for Psychiatric Conditions.

Mood disorders are the leading cause of disability worldwide and their incidence has significantly increased after the COVID-19 pandemic. Despite the continuous surge in the number of people diagnosed with psychiatric disorders, the treatment methods for these conditions remain limited. A significant number of people either do not respond to therapy or discontinue the drugs due to their severe side effects. Therefore, alternative therapeutic interventions are needed. Previous studies have shown a correlation between immunological alterations and the occurrence of mental health disorders, yet immunomodulatory therapies have been barely investigated for combating psychiatric conditions. In this article, we have reviewed the immunological alterations that occur during the onset of mental health disorders, including microglial activation, an increased number of circulating innate immune cells, reduced activity of natural killer cells, altered T cell morphology and functionality, and an increased secretion of pro-inflammatory cytokines. This article also examines key studies that demonstrate the therapeutic efficacy of anti-inflammatory medications in mental health disorders. These studies suggest that immunomodulation can potentially be used as a complementary therapy for controlling psychiatric conditions after careful screening of candidate drugs and consideration of their efficacy and side effects in clinical trials.

A hybrid cartilage extracellular matrix-based hydrogel/poly (ε-caprolactone) scaffold incorporated with Kartogenin for cartilage tissue engineering.

Despite extensive studies, hydrogels are unable to meet the mechanical and biological requirements for successful outcomes in cartilage tissue engineering. In the present study, beta cyclodextrin (ß-CD)-modified alginate/cartilage extracellular matrix (ECM)-based interpenetrating polymer network (IPN) hydrogel was developed for sustained release of Kartogenin (KGN). Furthermore, the hydrogel was incorporated within a 3D-printed poly (ε-caprolactone) (PCL)/starch microfiber network in order to reinforce the construct for cartilage tissue engineering. All the synthesized compounds were characterized by H1-NMR spectroscopy. The hydrogel/microfiber composite with a microfiber strand size and strand spacing of 300 µm and 2 mm, respectively showed a compressive modulus of 17.2 MPa, resembling the properties of the native cartilage tissue. Considering water uptake capacity, degradation rate, mechanical property, cell cytotoxicity and glycosaminoglycan secretions, ß-CD-modified hydrogel reinforced with printed PCL/starch microfibers with controlled release of KGN may be considered as a promising candidate for using in articular cartilage defects.

Effect of the Emulsion Solvent Evaporation Technique Cosolvent Choice on the Loading Efficiency and Release Profile of Anti-CD47 from PLGA Nanospheres.

INTRODUCTION: Side effects associated with using antibodies as therapeutics can limit systemic administration at the high concentrations often needed for therapeutic impact. Thus, therapeutic antibodies are usually considered for targeted delivery. Antibody encapsulation in polymeric nanoparticles via the emulsion-based nanofabrication methods typically yields low loading efficiencies. Therefore, the fabrication techniques need to be modified to maximize the loading efficiency of antibodies. In this work, we utilized various cosolvents with the emulsion solvent evaporation technique to improve the loading efficiency of anti-CD47, a therapeutic antibody used to block CD47 activity in atherosclerotic plaques and cancer lesions. METHODS AND RESULTS: The double emulsion solvent evaporation technique was used to fabricate anti-CD47-loaded polymeric nanoparticles. The primary oil phase solvent, chloroform, was doped with different cosolvents, including ethyl acetate, acetonitrile, ethanol, and methanol, to investigate the impact of cosolvents on the loading efficiency of anti-CD47. The release profile and loading efficiency were quantified by measuring the fluorescence signal of the released antibody. The activity of the antibody released from particles fabricated in the presence of the cosolvent was confirmed by quantifying its adherence to red blood cells. Ethyl acetate was the optimum cosolvent, improving the loading efficiency of anti-CD47 in poly(lactic-co-glycolic acid), PLGA, nanoparticles to 90% or higher, and the antibody was found to retain its activity after being released from nanoparticles. CONCLUSION: Our results demonstrate that a minimum amount of a cosolvent with minimal hydrophilicity can stabilize the antibody in the oil phase; thus, improving the antibody's loading efficiency significantly.

Potential antiviral effects of some native Iranian medicinal plants extracts and fractions against influenza A virus.

BACKGROUND: Influenza A virus (IAV) infection is a continual threat to the health of animals and humans globally. Consumption of the conventional drugs has shown several side effects and drug resistance. This study was aimed to screen some Iranian medicinal plants extracts and their fractions against influenza A virus. METHODS: Glycyrrhiza glabra (rhizome), Myrtus commonis (leaves), Melissa officinalis (leaves), Hypericum perforatum (aerial parts), Tilia platyphyllos (flower), Salix alba (bark), and Camellia sinensis (green and fermented leaves) were extracted with 80% methanol and fractionated with chloroform and methanol, respectively. The cytotoxicity of the compounds were determined by MTT colorimetric assay on MDCK cells. The effective concentrations (EC50) of the compounds were calculated from the MTT results compared to the negative control with no significant effects on cell viability. The effects of EC50 of the compounds on viral surface glycoproteins and viral titer were tested by HI and HA virological assays, respectively and compared with oseltamivir and amantadine. Preliminary phytochemical analysis were done for promising anti-IAV extracts and fractions. RESULTS: The most effective samples against IAV titer (P ≤ 0.05) were crude extracts of G. glabra, M. officinalis and S. alba; methanol fractions of M. communis and M. officinalis; and chloroform fractions of M. communis and C. sinensis (fermented) mostly in co- and pre-penetration combined treatments. The potential extracts and fractions were rich in flavonoids, tannins, steroids and triterpenoids. CONCLUSION: The outcomes confirmed a scientific basis for anti-influenza A virus capacity of the extracts and fractions from the selected plants for the first time, and correlated their effects with their phytochemical constituents. It is worth focusing on elucidating pure compounds and identifying their mechanism(s) of action.

Biodegradable, bile salt microparticles for localized fat dissolution.

Bile acids are proposed as therapeutic agents for various diseases, including liver diseases and obesity. However, oral or subcutaneous administration of a solubilized version of these drugs has limited efficacy and imposes unwanted side effects. Here, we describe a gold-templating method for fabricating stable, bile salt-cholate or deoxycholate-microparticles. The gold ions' reduction at the oil-water interface in a double emulsion solvent evaporation process enables a gold-bile salt interaction and the formation of bile salt particles. We demonstrate that composite microparticles release cholate/deoxycholate into solution via a surface erosion process. We illustrate these particles' capability to lyse adipocytes, both in vitro and in vivo, with minimal side effects, contrary to the Food and Drug Administration-approved salt solution that leads to severe inflammation and ulceration. Overall, particle-based cholate/deoxycholate opens opportunities for localized delivery of these salts, improving efficacy while minimizing side effects associated with oral and subcutaneous use.

Neutrophils preferentially phagocytose elongated particles-An opportunity for selective targeting in acute inflammatory diseases.

Polymeric particles have recently been used to modulate the behavior of immune cells in the treatment of various inflammatory conditions. However, there is little understanding of how physical particle parameters affect their specific interaction with different leukocyte subtypes. While particle shape is known to be a crucial factor in their phagocytosis by macrophages, where elongated particles are reported to experience reduced uptake, it remains unclear how shape influences phagocytosis by circulating phagocytes, including neutrophils that are the most abundant leukocyte in human blood. In this study, we investigated the phagocytosis of rod-shaped polymeric particles by human neutrophils relative to other leukocytes. In contrast to macrophages and other mononuclear phagocytes, neutrophils were found to exhibit increased internalization of rods in ex vivo and in vivo experimentation. This result suggests that alteration of particle shape can be used to selectively target neutrophils in inflammatory pathologies where these cells play a substantial role.

Modified two-step emulsion solvent evaporation technique for fabricating biodegradable rod-shaped particles in the submicron size range.

HYPOTHESIS: Though the emulsion solvent evaporation (ESE) technique has been previously modified to produce rod-shaped particles, it cannot generate small-sized rods for drug delivery applications due to the inherent coupling and contradicting requirements for the formation versus stretching of droplets. The separation of the droplet formation from the stretching step should enable the creation of submicron droplets that are then stretched in the second stage by manipulation of the system viscosity along with the surface-active molecule and oil-phase solvent. EXPERIMENTS: A two-step ESE protocol is evaluated where oil droplets are formed at low viscosity followed by a step increase in the aqueous phase viscosity to stretch droplets. Different surface-active molecules and oil phase solvents were evaluated to optimize the yield of biodegradable PLGA rods. Rods were assessed for drug loading via an imaging agent and vascular-targeted delivery application via blood flow adhesion assays. FINDINGS: The two-step ESE method generated PLGA rods with major and minor axis down to 3.2 µm and 700 nm, respectively. Chloroform and sodium metaphosphate was the optimal solvent and surface-active molecule, respectively, for submicron rod fabrication. Rods demonstrated faster release of Nile Red compared to spheres and successfully targeted an inflamed endothelium under shear flow in vitro and in vivo.

Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.

Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website.