Regulatory Challenges in Biomaterials: Focus on Medical Devices - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 258

TABlE 10.4
Some of the Studies Performed by the Nanotechnology Characterization Laboratory
to Address Critical Issues Regarding the Toxicity of Nanoparticles

Assay Category Questions to Address

In vitro
Hemolysis

Do nanoparticles change integrity of red blood cells?

Platelet aggregation Do nanoparticles interfere with cellular components of the blood

coagulation cascade?

Coagulation time Do nanoparticles cause changes in coagulation factors' function?

Complement activation Do nanoparticles activate the complement system?

CFU-GM Do nanoparticles cause myelosuppression (toxicity to bone

marrow precursors)?

Leukocyte proliferation Do nanoparticles have adverse effects on leukocyte proliferative

responses?

Uptake by macrophages Are nanoparticles internalized by specialized phagocytes?

Cytokine induction Do nanoparticles activate immune cells to elicit cytokine

production or interfere with that caused by known
immunogens?

Nitric oxide production Do nanoparticles induce oxidative stress? Indirect test for

potential endotoxin contamination.

Cytotoxicity of natural
killer cells

Do nanoparticles interfere with the ability of natural killer cells
to recognize and kill tumor target cells?

Endotoxin contamination Pyrogen contamination test

Microbial contamination Sterility test

Viral/mycoplasma
contamination

Sterility test

In vivo
Single-dose toxicity studies

Standard toxicity tests
Blood chemistry

Do nanoparticles cause toxicity to immune cells and organs?

Hematology Are there any indications for additional toxicity studies?

Histopathology Additional toxicity studies are conducted on a case-by-case basis

using weight-of-

Gross pathology evidence approach.

TDAR The test is receded for Is high predictability for human models.

Host-resistance studies
Evaluation of cell-
mediated immunity

These tests are recommended for (1) testing the potential effects
that particles might have on host resistance towards pathogens
and tumor cells and (2) to check for contact sensitization and
delayed type hypersensitivity reactions.

Repeated dose toxicity study
Immunogenicity

Do nanoparticles elicit particle specific immune response?

Reprinted with permission from Nature Publishing Group, 2007. (Drobovolskaia, M.A and
McNeil, S. 2007. Immunological properties of nanoscale materials. Nat. Nanotechnol. 2: 469-478.)