Nanoparticle physicochemical properties determine the activation of intracellular complement.

The complement system plays an essential role in both innate and adaptive immunity. The traditional understanding of this system comes from studies investigating complement proteins produced by the liver and present in plasma to "complement" the immune cell-mediated response to invading pathogens. Recently, it has been reported that immune cells including, but not limited to, T-cells and monocytes, express complement proteins.

Analysis of Pro-inflammatory Cytokine and Type II Interferon Induction by Nanoparticles.

Cytokines, chemokines, and interferons are released by the immune cells in response to cellular stress, damage and/or pathogens, and are widely used as biomarkers of inflammation. Certain levels of cytokines are needed to stimulate an immune response in applications such as vaccines or immunotherapy where immune stimulation is desired. However, undesirable elevation of cytokine levels, as may occur in response to a drug or a device, may lead to severe side effects such as systemic inflammatory response syndrome or cytokine storm.

Analysis of Complement Activation by Nanoparticles.

The complement system is a group of proteins, which function in plasma to assist the innate immunity in rapid clearance of pathogens. The complement system also contributes to coordination of the adaptive immune response. Complement Activation Related Pseudo Allergy or CARPA is a life-threatening condition commonly reported with certain types of drugs and nanotechnology-based combination products.

In Vitro Analysis of Nanoparticle Effects on the Zymosan Uptake by Phagocytic Cells.

This chapter provides a protocol for analysis of nanoparticle effects on the function of phagocytic cells. The protocol relies on luminol chemiluminescence to detect zymosan uptake. Zymosan is an yeast particle which is typically eliminated by phagocytic cells via the complement receptor pathway.

In Vitro Assessment of Nanoparticle Effects on Blood Coagulation.

Blood clotting is a complex process which involves both cellular and biochemical components. The key cellular players in the blood clotting process are thrombocytes or platelets. Other cells, including leukocytes and endothelial cells, contribute to clotting by expressing the so-called pro-coagulant activity (PCA) complex on their surface.

Updated Method for In Vitro Analysis of Nanoparticle Hemolytic Properties.

Hemolysis is damage to red blood cells (RBCs), which results in the release of the iron-containing protein hemoglobin into plasma. An in vitro assay was developed and described earlier for the analysis of nanoparticle hemolytic properties. Herein, we present a revised version of the original protocol.

Detection of Bacterial Contamination in Nanoparticle Formulations by Agar Plate Test.

Bacterial contamination can confound the results of in vitro and in vivo preclinical tests. This protocol describes a procedure for detection of microbial contamination in nanotechnology-based formulations. Nanoparticle samples and controls are spread on the surface of agar and growth of bacterial colonies is monitored after 72 h of incubation.

Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future.

Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products.

Induction of oxidative stress by Taxol® vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA.

Unlabelled: Understanding the ability of cytotoxic oncology drugs, and their carriers and formulation excipients, to induce pro-inflammatory responses is important for establishing safe and efficacious formulations. Literature data about cytokine response induction by the traditional formulation of paclitaxel, Taxol®, are controversial, and no data are available about the pro-inflammatory profile of the nano-albumin formulation of this drug, Abraxane®. Herein, we demonstrate and explain the difference in the cytokine induction profile between Taxol® and Abraxane®, and describe a novel mechanism of cytokine induction by a nanosized excipient, Cremophor EL, which is not unique to Taxol® and is commonly used in the pharmaceutical industry for delivery of a wide variety of small molecular drugs.

Inhibition of phosphoinositol 3 kinase contributes to nanoparticle-mediated exaggeration of endotoxin-induced leukocyte procoagulant activity.

Aim: Disseminated intravascular coagulation is an increasing concern for certain types of engineered nanomaterials. Recent studies have shed some light on the nanoparticle physicochemical properties contributing to this toxicity; however, the mechanisms are poorly understood. Leukocyte procoagulant activity (PCA) is a key factor contributing to the initiation of this toxicity.

Nanoparticles and the blood coagulation system. Part II: safety concerns.

Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern.

Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology.

Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine.