Scott McNeil, Ph.D.

1
Public Meeting on Nanotechnology Materials in
FDA-Regulated Products October 10, 2006
Preclinical Characterization of Nanoparticles

• Scott McNeil, Ph.D.
• ncl_at_ncifcrf.gov
• http//ncl.cancer.gov

2
Cancer Nanotechnology Program

• Managed by Office of Technology and Industrial
  Relations (OTIR), NCI
• Launched on Sept 13th, 2004
• Website http//nano.cancer.gov
• Consensus among cancer researchers that
  significant obstacles must be overcome in order
  to translate nano into the clinical realm
• Critical lack of available standards
• 1st principles characterization
• Perceived regulatory uncertainty

3
Nanotechnology CharacterizationLaboratory (NCL)
NCL Concept of Operations
FDA
NCL is a formal collaboration among NCI, FDA and
NIST
4
A Different Approach Is Needed

• Physicochemical Parameters
• Composition
• Physical properties
• Chemical properties
• Identification
• Quality
• Purity
• Stability

Small molecules

• Elemental analysis
• Mass
• NMR
• UV-Vis
• IR
• HPLC
• GC
• Polarimetry

Same parameters different/additional
characterization methods
5
Influence of Surface Chemistry/Charge
G4 PEG
LLC-PK1 24 hr Cytotoxicity
G6 PEG
MTT Viability Assay
G6 OH
140
G6 NH2
120
G6 CO2H
100
80
Dendrimer
Control
60
40
20
0
0.0001
0.001
0.01
0.1
1
10
Dose (mg/mL)
NCL is working with FDA to identify parameters
that contribute to biocompatibility and toxicity.
6
Particle Size in a Biological Context
No Incubation
Serum
DLS Size
50nm
DLS Size
50nm
56nm
113nm

Characterization should be interdisciplinary, and
conducted under biologically relevant conditions
DLS Size
DLS Size
30nm
30nm
82nm
36nm
7
Summary

• NCL is a collaboration among NCI, FDA and NIST
• Nanomaterials intended for medical applications
  may require an alternate toolset for
  characterization
• Preclinical testing indicates that multiple
  physico-chemical parameters influence
  biocompatibility and toxicity
• Key parameters include size, surface chemistry,
  and charge
• Elucidation of structure activity relationships
  requires an interdisciplinary approach
• Data does not support generalizations

Contact Info Scott E. McNeil ncl_at_ncifcrf.gov (301
) 846-6939 http//ncl.cancer.gov