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Nano-Sized Drug Delivery. Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles. Topic of Today’s Lecture. This talk will focus on my research on combining synthetic polymers with proteins from Nature to produce nano-sized medicines.

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nano sized drug delivery
Nano-Sized Drug Delivery

Prof. Heather D. Maynard

Department of Chemistry and Biochemistry

University of California, Los Angeles

topic of today s lecture
Topic of Today’s Lecture

This talk will focus on my research on combining synthetic polymers with proteins from Nature to produce nano-sized medicines

outline of today s lecture
Outline of Today’s Lecture
  • What is nano?
  • Polymers are everywhere!
  • Why nanosized carriers are important in medicine
  • Protein-polymer nano-therapeutics
outline of today s lecture4
Outline of Today’s Lecture
  • What is nano?
  • Polymers are everywhere!
  • Why nanosized carriers are important in medicine
  • Protein-polymer nano-therapeutics
what is nano
What is Nano?
  • Nanoscience is the study of objects measured in nanometers
    • 1-billionth of a meter
    • ~80,000 times smaller than the diameter of a single human hair
slide6

Closer Look at a Human Hair

Width of this line is 100 nm

http://www.aber.ac.uk/bioimage/image/uwbl-0411-w.jpg

what is nano7
What is Nano?
  • Nanoscience is the study of objects measured in nanometers
    • 1-billionth of a meter
    • ~80,000 times smaller than the diameter of a single human hair
    • New properties emerge at the nanoscale
      • Size and shape matter
slide8

Super-Repellent Nano-Materials

http://cjmems.seas.ucla.edu/members/changhwan/main.html

http://www.engineer.ucla.edu/magazine/fall06/noslip.html

slide10

Nano-Finger Tips Allow Geckos to Stick

http://robotics.eecs.berkeley.edu/~ronf/Gecko/index.html

slide12

Super Adhesive Nano-Materials

Synthetic nano-materials can exhibit strong adhesion similar to gecko fingers

Yurdumarkan et al, Chem. Commun. 2005, 3799-3801

how nano effects you
How Nano Effects You

Nanotech products are already on the market

slide14

According to the National Nanotechnology Initiative (NNI), “The worldwide workforce necessary to support the field of nanotechnology is estimated at 2 million by 2015”*

UCLA is at the forefrontof nanotechnology research and education!!

There are many course that are now offered on the subject, including my BioNanotechnology Course (Chem140/240)

*http://www.nano.gov/html/edu/home_edu.html

outline of today s lecture15
Outline of Today’s Lecture
  • What is nano?
  • Polymers are everywhere!
  • Why nanosized carriers are important in medicine
  • Protein-polymer nano-therapeutics
polymers
Polymers
  • Big molecules made of repeating units of smaller molecules
    • Small molecules are called “monomers”
    • Monomers link together like a chain
    • Results in new and exciting properties!!
polymers everywhere in daily life
Polymers – Everywhere in Daily Life

DNA

Starch

Cellulose

Rubber

HDPE

Teflon

Nylon

PVC

slide19

Data from 2004 showed that plastics industry including suppliers accounted for 2.1 million jobs and $438 billion in shipments*

It is estimated that half of all industrial chemists work in some area of polymer chemistry**

Therefore it is vital that chemistry students learn about polymers. At UCLA we teach the chemical aspects of polymers in a devoted course (Chem 181), as well as in the Sophomore Organic Chemistry Series (Chem 30C)

* http://www.gcx-online.com/gcx/article.asp?magarticle_id=561

**Zumdahl, S. S. Chemical Principles; D. C. Heath and Co.’ Lexington, Massachusetts, 1992, p. 947

slide20

Different Shapes and Sizes

The way the monomers are connected has a very large influence on the resultant properties

Duncan Nature Reviews2003, 2, 347-360

polymers in medicine

Transdermal Patch

Microspheres

Biodegradable Polymer

Drug: Fentanyl (pain killer)

Nicotine

Name: Duragesic, Nicoderm,

Habitrol, Prostep, Nicotrol

Dosis: 72 hours (fentanyl)

Biodegradable Polymer

Drug: luteinizing hormone-releasing

hormone (LHRH) analog

Name: Decapeptyl, Lypron depot

Advanced prostate cancer

Dose: ~3 months

Polymers in Medicine

Moses, M.; Brem, H.; Langer, R. Cancer Cell, 2003, 4, 337

outline of today s lecture22
Outline of Today’s Lecture
  • What is nano?
  • Polymers are everywhere!
  • Why nanosized carriers are important in medicine
  • Protein-polymer nano-therapeutics
nano in medicine
Nano in Medicine
  • A nano sized “pill”
  • They target tumors to deliver cancer drugs
  • Nano “pills” can be modified to hone to a other tissues in the body to deliver drugs for other diseases
slide24

Tumors Grow Blood Vessels

Tumors need blood to grow larger than ~2mm in size

Peer, D, et al. Nature Nanotechnology 2007, 2, 751-760

epr effect
EPR Effect
  • Tumors have “leaky” blood vessels, which allow relatively large nano-sized “pills” to enter. This is called Enhanced Permeability and Retention (EPR) Effect . Normal blood vessels are not “leaky” and nano-particles are prevented from entering. This allows one to selectively target tumors.

Duncan, R. Nature Reviews Cancer 2006, 6, 688-701

slide26

Polymers Form Nano “Pills”

Duncan Nature Reviews2003, 2, 347-360

slide27

Nano Carriers Example: AmBisome

Drug: amphotericin B

antifungal infections for cancer patients

Name of product: AmBisome

Approved in 1997

Moses, M.; Brem, H.; Langer, R. Cancer Cell, 2003, 4, 337

slide28

Nano Carriers Example: Doxil

Drug: doxorubicin

Chemotherapy agent for ovarian cancer

Name of product: Doxcil

Reduced cardiotoxicity

Http://www.doxil.com

slide29

Nano Carriers Example: Abraxane

Drug: Paclitaxel

Chemotherapy for breast cancer

Name of product: Abraxane

Approved in 2005 ($134 million in sales that year)*

Chemotherapeutic bound to protein nano-particle

Http://www.abraxisbio.com

*Data from Small Times

outline of today s lecture30
Outline of Today’s Lecture
  • What is nano?
  • Polymers are everywhere!
  • Why nanosized carriers are important in medicine
  • Protein-polymer nano-therapeutics
slide32

What is a Protein?

Proteins are natural polymers found in the body that are made up of many small units that are called amino acids.

Protein comes from Greek word proteios meaning primary

Proteins are critical to life and

serve many different functions

Structure of protein called myoglobin which delivers oxygen to muscle tissues

http://en.wikipedia.org/wiki/Protein

slide33

Protein Function

Proteins regulate the function and structure of cells, tissues and organs

Examples

Hemoglobin carries oxygen through the body.

Melaningives skin pigmentation and the iris color.

Keratin provides structure of hair and nails.

Serum Albuminmaintains blood pressure.

Alcohol Dehydrogenasebreaks down alcohol in the liver.

commercial protein therapeutics
Commercial Protein Therapeutics

Proteins are highly evolved and specific, so they make excellent drugs

  • Insulin
    • Helps to regulate blood glucose levels for people with diabetes.
  • Interferon-a(Intron A, Roferon)
    • Used for the treatment of chronic hepatitis C in adults.
  • Erythropoietin (Procrit, Epogen)
    • Used to treat anemia caused by chemotherapy, HIV or kidney disease.
    • Glycoprotein which stimulates the production of red blood cells.
proteins degrade
Proteins Degrade

Proteins must be injected – they are not taken orally

Proteins rapidly degrade in the body by natural mechanisms

This means that in order to have a sustained affect – the patient must endure many injections

one solution
One Solution

By attaching polymer chains, the protein is protected from degradation, circulates longer in the blood stream, has a decreased immune response, and lasts longer in the body

This means fewer injections for the patient and better compliance

slide37

Advantages of Protein-Polymer Conjugates

Protein-polymer therapeutics are nano-sized drugs with many advantages

Francesco M. Veronese et al., Drug Discovery Today2005, 10, 1451-1458

slide38

PEG – a Special Polymer

polyethylene glycol

or polyethylene oxide

or PEG

or PEO

  • FDA approved
  • Protein resistant
  • Water soluble
  • Low immune response
  • Biocompatible
slide39

Protein-Polymer Conjugates

Interferon

a

Attaching polymers to proteins is called “PEGylation”:

Interferon

a

+

Polyethylene glycol

PEG Intron A

PEG Intron requires only 1 injection per week, compared to three injections per week of Intron A

Data from the FDA

slide40

Protein-Polymer Conjugates on Market

Many of these nano-drugs are clinically used

www.debio.com/e/pdf/peg_e.pdf

Duncan Nature Reviews Cancer, 2006

slide41

Maynard Group Research

My group focuses on developing new synthetic methods to generate this important class of materials, such that the resulting protein-polymer conjugates have superior properties

Heredia & Maynard, OBC, 2007