8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 1/9

Cancer Nanotechnology:

New Opportunities forTargeted Therapies

FDA Public MeetingOctober 10, 2006

Piotr Grodzinski, Ph.D.

Director, Nanotechnology for Cancer Programs

Office of Technology and Industrial Relations

National Cancer Institute

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 2/9

• 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

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 3/9

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) 

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 4/9

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)

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 5/9

Uncertainties of Moving Multi-FunctionalNanoparticles 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

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 6/9

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

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 7/9

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 materialmanufacturing (GMP)

• Provide studies towards

IND filing• Initiate Phase 0/Phase Itrials

Challenges:

• High cost

• Low interest in academicenvironment, where most of theinnovation resides

• Partnerships with the industryneeded

NanotechnologyAlliance, NCL

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 8/9

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

biomedicalapplications

Preclinical studies

8/11/2019 06n-0107-ts00018-grodzinski (1)

http://slidepdf.com/reader/full/06n-0107-ts00018-grodzinski-1 9/9

Interagency Collaborations

• Characterization

• Critical path

development• Training

• Public Interface

• Interpret Dataon Environment,

Health andSafety

• Shared Dataand Platforms

• Standards/PrecisionMeasurement Capabilities

• NanobiotechnologyTraining