Download Converting Elastin-like Polypeptides(ELP) Aggregate to Soluble Form

Converting Elastin-like
Polypeptides(ELP) Aggregate to
Soluble Form
Client: Darin Furgeson PhD
School of Pharmacy
Dhaval Desai (Leader)
Lee Linstroth (Communicator)
Malini Soundarrajan (BSAC)
Nathan Kleinhans (BWIG)
Advisor: Naomi Chesler PhD
Department of Biomedical Engineering
Overview
Problem Statement
Background
Design Specifications
Alternative design ideas
Design matrix
Future work
Questions
Problem Statement
Elastin-Like Polypeptides (ELPs) may serve as
promising drug-delivery agents to treat various
types of cancers. In order for our client, Dr.
Furgeson, to conduct research on ELPs, soluble
form of ELP is required. After harvesting ELPs
from bacteria, ELPs become aggregated. The
purpose of this project is to design a device that
will make it easy to convert ELP aggregate into
soluble form.
Background
 Current Cancer Treatments
Hormonal Therapy:
 Remove hormone producing organs
 Inhibit hormone-receptor binding with antagonists
 Affect other organs in the body
Chemotherapy
 Interfere with the growth and reproductive processes in
cancer cells
 Destroy normal cells; not tissue specific
Radiation therapy
 Use of X-rays, gamma rays, or radioactive implants
 Damage the DNA in cancer cells
 Harm normal cells
Background
ELP is a promising non-viral gene/drug
carrier
Non-immunogenic
Inverse Temperature Transition
Aggregates above Tt and solubilizes below Tt
Hydrophobic
Background
Design Specification
Resolubilize in PBS
Automated
Efficient
80% product yield
Less than 20 lbs
Fits in a 1m X 1m X 0.5m lab space
Must operate below Tt
Brush Model
 Commercially
available test tube
brush: Nylon
Bristles: 20 mm long,
35 mm diameter
Shaft: 150 mm long,
powered by motor
 Scrape ELP off the
sides
Brush Model
 Pros
Easy to assemble
High surface area of
bristles exposed to the
aggregate for ELP-PBS
mixing
 Cons
Difficult to clean
Product loss
Helix Model
 Two intertwining
spirals form a helix
 Blades soldered
within the helix to
break apart aggregate
 Made of low gauge
wire or thin sheet
metal
 Powered by external
motor
Helix Model
 Pros
Resembles current
industrial mixer
Easily cleaned
Cost effective
 Cons
Difficult to manufacture
Possible low product
yield
Safety concerns
Dual Scraper Model
 Utilized metal scraper
with slits
 Scrapers are in
contact with the side
of the tube
 Slits aid in agitating
solution
Dual Scraper Model
 Pros
Maximizes product
resolubilization
Agitates solution
 Cons
Difficult to manufacture
ELP might adhere to
the curved scrapers
Design Matrix
Criteria
Brush
Model
Helix
Model
Dual
Scraper
Model
Ease of Cleaning 2
7
6
Product Yield
2
5
7
Cost
8
6
5
Ease of
Manufacturing
8
4
7
Prototype Life
2
6
8
Total
22
28
33
Future Work
Final design/modifications
Choose materials
Build prototype
Extensive testing with ELP
References
 Betre H, Setton LA, Meyer DE, Chilkoti A.
Characterization for genetically engineered elastin-like
polypeptide for cartilaginous tissue repair.
Biomacromolecules. 2002 Sep-Oct, 3(5): 910-6.
 Chilkoti A, Dreher MR, Meyer DE, Design of thermally
responsive recombinant polypeptide carriers for targeted
drug delivery. Adv. Drug Deliv Rev. 2002 Oct 18; 54(8):
1093-111. Review
 Chilkoti A, Dreher MR, Meyer DE, Raucher D. Targeted
drug delivery by thermally responsive polymers. Adv
Drug Deliv. Rev. 2002 Sep 13; 54(5): 613-30. Review