1. Cancer Nanotechnology:
New Opportunities for
Targeted Therapies
FDA Public Meeting
October 10, 2006
Piotr Grodzinski, Ph.D.
Director, Nanotechnology for Cancer Programs
Office of Technology and Industrial Relations
National Cancer Institute
2. • Provides multi-functionality: targeting,
delivery, reporting
• Provides improved therapeutic index
• Provides lowered toxic side effects
• Delivers multiple drugs directly to tumor site
• Enables nucleic acid delivery
• Enables non-drug therapies (photothermal,
photodynamic)
Nanotechnology-based Drug Delivery:
Key Benefits
Nanomaterial characterization: Responsible, Systematic, Standardized
3. Multi-Functional Nanoparticle-based Therapies
• Multi-functional platforms:
• Targeting
• Delivery
• Reporting, biosensing
In one package
Free drug formulations do not
possess multi-functional
characteristics
First generation of nano-delivered
drugs (no targeting) approved by
FDA – Abraxane®
M. Ferrari, Nature Reviews 5, 161 (2005)
4. Nanoshells:
Photothermal therapy
N. Halas, J. West et al,
Ann Biomed Eng. 34, 15 (2006)
Dendrimers:
Targeted delivery of methotrexate
Nanoparticle-based Therapies:
Different Approaches
J. Baker, et al., Cancer Res. 65, 5317
(2005)
5. Uncertainties of Moving Multi-Functional
Nanoparticles to the Clinic
• Differences exist between the development and regulatory pathway
for multi-functional nanoparticles and “traditional” drugs and
devices. Need to:
• Define the classification (decision tree) in order to determine the
characterization process ahead of the submission
• Provide interfaces within the regulatory agencies
• Establish uniform, publicly available guidelines for the investigators
• Determination if therapy is new when it uses an existing drug on a
novel delivery platform is a challenge
• Gap exists between technology development in an academic setting
and further technology maturation through clinical development and
regulatory approval
6. NCI Strategy:
Alliance for Nanotechnology in Cancer
A comprehensive, systematized initiative encompassing the public and
private sectors, designed to accelerate the use of the best capabilities
of nanotechnology to cancer applications
• Centers of Cancer Nanotechnology Excellence (CCNEs) and
Cancer Nanotechnology Platform Partnerships (CNPPs)
• To develop novel technologies to deliver drugs more effectively
• To develop new, highly sensitive and specific diagnostic techniques
• Nanotechnology Characterization Laboratory (NCL)
• To develop a standardized assay cascade for preclinical characterization
• To identify physical parameters and structure-activity relationships for
biocompatibility
• Not to address animal efficacy, SAR, PK or PD studies, or manufacturing
7. Next step
Adapted from Challenge and Opportunity on
the Critical Path to New Medical Products
(http://www.fda.gov/oc/initiatives/criticalpath/
whitepaper.html)
Nanoparticle Translation Mechanism:
From Early Development to the Clinic
Opportunities:
• Leverage NCL
capabilities
• Scale up the material
manufacturing (GMP)
• Provide studies towards
IND filing
• Initiate Phase 0/Phase I
trials
Challenges:
• High cost
• Low interest in academic environment,
where most of the innovation resides
• Partnerships with the industry needed
Nanotechnology
Alliance, NCL
8. Nanotechnology:
Environmental and Safety Considerations
• Hazard identification
• In vitro toxicity
• Acute in vivo toxicity
• Subchronic/chronic toxicity
• Route of exposure
• Dose response
• External dose
• Internal dose
• Biologically effective dose
• Exposure assessment
• Human exposure
Nanomaterials
production
Chronic exposure
of the worker
Nanomaterials
use for
biomedical
applications
Preclinical studies
9. Interagency Collaborations
• Characterization
• Critical path
development
• Training
• Public Interface
• Interpret Data
on Environment,
Health and
Safety
• Shared Data
and Platforms
• Standards/Precision
Measurement Capabilities
• Nanobiotechnology
Training
10. Interagency Collaborations
• Characterization
• Critical path
development
• Training
• Public Interface
• Interpret Data
on Environment,
Health and
Safety
• Shared Data
and Platforms
• Standards/Precision
Measurement Capabilities
• Nanobiotechnology
Training
