Nanoparticle Immunotoxicity Workshop

   Workshop Overview

The immune system operates at the nanoscale, as does all of biology where macromolecules interact to perform the functions necessary for life. Nanotechnology, the manipulation of nanoscale objects, is finding growing applications in the pharmaceutical industry to engineer nanoparticle-based drugs and diagnostics. These nanoscale formulations are often specifically engineered to either target or avoid interaction with the immune system. Unlike many traditional pharmaceutics, nanoparticles interfere with most standard immunological in vitro tests. The mechanism of interference varies with the type of nanoparticle. For instance, certain nanoparticles absorb light and interfere with in vitro colorimetric methods. Many nanoparticles have catalytic properties and can enhance assays that rely on enzymatic reactions, generating false-positive results. Assays routine to the preclinical characterization of conventional pharmaceuticals, such as the Limulus amebocyte lysate (LAL) test for endotoxin contamination detection may yield spurious results when applied to nanoparticle samples. Cytokine secretion tests and the in vivo rabbit pyrogen test are also not always informative for the pyrogenicity assessment of nanoparticles. Approaches for in vivo analysis of nanoparticle-mediated immunotoxicity require better understanding and harmonization.

The purpose of this workshop is to review the current set of immunotoxicity characterization guidelines (e.g. ISO 10993-4, ICH S8), and in vitro and in vivo tests (e.g. LLNA and PFC), and their applicability to nanoparticle formulations.

   Workshop Objectives

• To discuss approaches to identify and overcome nanoparticle interference with traditional in vitro immunological assays.
• To discuss sterility/pyrogenicity evaluation of nanoparticle-based products in cases when nanoparticles interfere with standard tests.
• To discuss applicability of the ISO 10993-4 standard to nanoparticle based products. A sub-aim is to identify differences between nanoparticles and traditional pharmaceutics and devices and the relevance of hematocompatibility tests to biomedical nanoparticles.
• To discuss applicability of the ICH S8 to nanomaterials. A sub-aim is to determine the need for additional immunotoxicity tests specific to nanomaterials, and to understand how LLNA and PFC tests correlate with nanoparticle-mediated immunotoxicity.

   Workshop Agenda

Each presentation will be followed by a 10 min Q&A session