Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry...
-
Upload
ebony-lovely -
Category
Documents
-
view
217 -
download
0
Transcript of Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry...
![Page 1: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/1.jpg)
Nano-Sized Drug Delivery
Prof. Heather D. Maynard
Department of Chemistry and Biochemistry
University of California, Los Angeles
![Page 2: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/2.jpg)
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
![Page 3: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/3.jpg)
Outline of Today’s Lecture
1. What is nano?2. Polymers are everywhere!3. Why nanosized carriers are
important in medicine4. Protein-polymer nano-therapeutics
![Page 4: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/4.jpg)
Outline of Today’s Lecture
1. What is nano?2. Polymers are everywhere!3. Why nanosized carriers are
important in medicine4. Protein-polymer nano-therapeutics
![Page 5: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/5.jpg)
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
![Page 6: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/6.jpg)
http://www.aber.ac.uk/bioimage/image/uwbl-0411-w.jpg
Closer Look at a Human Hair
Width of this line is 100 nm
![Page 7: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/7.jpg)
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
![Page 8: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/8.jpg)
Super-Repellent Nano-Materials
http://www.engineer.ucla.edu/magazine/fall06/noslip.htmlhttp://cjmems.seas.ucla.edu/members/changhwan/main.html
![Page 9: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/9.jpg)
Geckos Walk on Walls
![Page 10: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/10.jpg)
Nano-Finger Tips Allow Geckos to Stick
http://robotics.eecs.berkeley.edu/~ronf/Gecko/index.html
![Page 11: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/11.jpg)
Man-Made Geckos
![Page 12: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/12.jpg)
Super Adhesive Nano-Materials
Yurdumarkan et al, Chem. Commun. 2005, 3799-3801
Synthetic nano-materials can exhibit strong adhesion similar to gecko fingers
![Page 13: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/13.jpg)
Nanotech products are already on the market
How Nano Effects You
![Page 14: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/14.jpg)
*http://www.nano.gov/html/edu/home_edu.html
UCLA is at the forefront of nanotechnology research and education!!
There are many course that are now offered on the subject, including my BioNanotechnology Course
(Chem140/240)
According to the National Nanotechnology Initiative (NNI), “The worldwide workforce
necessary to support the field of nanotechnology is estimated at 2 million by
2015”*
![Page 15: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/15.jpg)
Outline of Today’s Lecture
1. What is nano?2. Polymers are everywhere!3. Why nanosized carriers are
important in medicine4. Protein-polymer nano-therapeutics
![Page 16: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/16.jpg)
“I just want to say one word to you – just one word…. plastics.”
The Graduate (1967)
![Page 17: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/17.jpg)
• 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
![Page 18: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/18.jpg)
Starch Rubber
Teflon
DNA
HDPE
Cellulose
Nylon PVC
Polymers – Everywhere in Daily Life
![Page 19: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/19.jpg)
It is estimated that half of all industrial chemists work in some area of polymer chemistry**
* 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
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)
Data from 2004 showed that plastics industry including suppliers accounted for 2.1
million jobs and $438 billion in shipments*
![Page 20: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/20.jpg)
Duncan Nature Reviews 2003, 2, 347-360
Different Shapes and Sizes
The way the monomers are connected has a very large influence on the resultant properties
![Page 21: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/21.jpg)
Transdermal Patch
Biodegradable PolymerDrug: Fentanyl (pain killer) NicotineName: Duragesic, Nicoderm, Habitrol, Prostep, Nicotrol Dosis: 72 hours (fentanyl)
Microspheres
Biodegradable PolymerDrug: luteinizing hormone-releasing hormone (LHRH) analogName: Decapeptyl, Lypron depotAdvanced prostate cancerDose: ~3 months
Polymers in Medicine
Moses, M.; Brem, H.; Langer, R. Cancer Cell, 2003, 4, 337
![Page 22: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/22.jpg)
Outline of Today’s Lecture
1. What is nano?2. Polymers are everywhere!3. Why nanosized carriers are
important in medicine4. Protein-polymer nano-therapeutics
![Page 23: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/23.jpg)
• 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
Nano in Medicine
![Page 24: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/24.jpg)
Peer, D, et al. Nature Nanotechnology 2007, 2, 751-760
Tumors Grow Blood Vessels
Tumors need blood to grow larger than ~2mm in size
![Page 25: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/25.jpg)
Duncan, R. Nature Reviews Cancer 2006, 6, 688-701
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.
![Page 26: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/26.jpg)
Polymers Form Nano “Pills”
Duncan Nature Reviews 2003, 2, 347-360
![Page 27: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/27.jpg)
Drug: amphotericin B antifungal infections for cancer patients
Name of product: AmBisomeApproved in 1997
Moses, M.; Brem, H.; Langer, R. Cancer Cell, 2003, 4, 337
Nano Carriers Example: AmBisome
![Page 28: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/28.jpg)
Drug: doxorubicin Chemotherapy agent for ovarian cancer
Name of product: DoxcilReduced cardiotoxicity
Http://www.doxil.com
Nano Carriers Example: Doxil
![Page 29: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/29.jpg)
Drug: Paclitaxel Chemotherapy for breast cancer
Name of product: AbraxaneApproved in 2005 ($134 million in sales that year)*
Chemotherapeutic bound to protein nano-particle
Nano Carriers Example: Abraxane
Http://www.abraxisbio.com *Data from Small Times
![Page 30: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/30.jpg)
Outline of Today’s Lecture
1. What is nano?2. Polymers are everywhere!3. Why nanosized carriers are important
in medicine4. Protein-polymer nano-therapeutics
![Page 31: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/31.jpg)
What is a Protein?
![Page 32: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/32.jpg)
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
What is a Protein?
http://en.wikipedia.org/wiki/Protein
Structure of protein called myoglobin which delivers oxygen to muscle tissues
![Page 33: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/33.jpg)
Proteins regulate the function and structure of cells, tissues and organs
ExamplesHemoglobin carries oxygen through the body.Melanin gives skin pigmentation and the iris color.Keratin provides structure of hair and nails.Serum Albumin maintains blood pressure.Alcohol Dehydrogenase breaks down alcohol in the liver.
Protein Function
![Page 34: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/34.jpg)
Commercial Protein Therapeutics
• Insulin– Helps to regulate blood glucose levels for people with diabetes.
• Interferon- (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 are highly evolved and specific, so they make excellent drugs
![Page 35: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/35.jpg)
Proteins DegradeProteins 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
![Page 36: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/36.jpg)
One SolutionBy 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
![Page 37: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/37.jpg)
Francesco M. Veronese et al., Drug Discovery Today 2005, 10, 1451-1458
Advantages of Protein-Polymer Conjugates
Protein-polymer therapeutics are nano-sized drugs with many advantages
![Page 38: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/38.jpg)
• FDA approved • Protein resistant• Water soluble• Low immune response• Biocompatible
OO
OO
On
polyethylene glycolor polyethylene oxideor PEG or PEO
PEG – a Special Polymer
![Page 39: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/39.jpg)
Interferon
OO
OO
On
+Polyethylene glycol
Interferon
PEG Intron A
Protein-Polymer Conjugates
PEG Intron requires only 1 injection per week, compared to three injections per week of Intron A
Data from the FDA
Attaching polymers to proteins is called “PEGylation”:
![Page 40: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/40.jpg)
Duncan Nature Reviews Cancer, 2006
Protein-Polymer Conjugates on Market
www.debio.com/e/pdf/peg_e.pdf
Many of these nano-drugs are clinically used
![Page 41: Nano-Sized Drug Delivery Prof. Heather D. Maynard Department of Chemistry and Biochemistry University of California, Los Angeles.](https://reader034.fdocuments.net/reader034/viewer/2022051415/56649caf5503460f94973edd/html5/thumbnails/41.jpg)
Heredia & Maynard, OBC, 2007
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