Research and Design of

Industrial Scale Reactor for

Paxlitaxel Loaded PLGA
Students: Sara Peterson, Sarah Chaikind, Stephanie Lundgren, Emily Gee

Faculty Advisor: Dr. Mike Zhang

Professor, Biological Systems Engineering Department, Virginia Tech

External Advisor: Dr. Matthew Dickson

Associate Director R&D, MedImmune 1
Problem Statement

Design an industrial scale reactor system to meet the

projected need of 260,000 cases of breast cancer in
the United States in 2017.

Mix Paclitaxel, with the FDA approved biodegradable

nanoparticle, PLGA, for targeted drug delivery

Eliminate adverse effects on the body caused by

chemotherapy while still providing the same efficacy
of treatment 2
Constraints Standards
One year run time under $12B 1.Specification for bioreactor design for
production of recombinant protein
Production of PLGA nanoparticles between 160 and 170 in
diameter 2.Nanoparticle measurements and standards
for use in biomedical applications and health
PLGA loaded with Paclitaxel at 80% encapsulation
efficiency 3.Proposed design standards for bioreactor
design
Criteria
4.Good clinical practices for oncology
Scale up difficulties associated with nanoparticle production treatments

Very high target population size - 18 systems needed to 5.Drug delivery and nanoparticles applications
service U.S. population and hazards standards

Maintenance of nanoparticles through process to ensure

correct size and drug loading of each particle to meet FDA
requirements

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Drug Loading Process

Two independently mixed vessels

containing the organic and aqueous
solutions are fed into a mixing reactor
After 36 hours of mixing, solution to a
distillation vacuum to evaporate away
DMSO
Centrifuge
Spray drying for packaging

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Industrial Downstream Unit Operations

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3 Reactor System Overview
Inventor image of all three reactors together -- Sara will add

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Reactor 1:The Organic Phase (500 L Tank)
Inventor Image of reactor 1 -- Sara will add

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Reactor 2: the Aqueous Phase (4000 L Tank)
Inventor Image of reactor 2 -- Sara will add

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Reactor 3: Combined Mixing Phase (5000 L Tank)
Inventor Image of reactor 3 -- Sara will add

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Our 3 Reactor Design Accomplishes..
1. Scales-up and industrializes a current laboratory only practice

2. Optimizes the Paclitaxel loaded PLGA process by using ideal solvents and a
surfactant resulting in maximized drug loading efficiency (80%) above current
laboratory standards of around 40%

3. Impeller design minimizes variation in nanoparticle size (160 - 170 nm) by

maximizing shear stress in large mixing tank

4. System of reactors allows for the separate mixing of aqueous and organic
phases prior to combination, homogenous mixing is achieved at every stage

5. Divider in the 5,000 L mixing reactor allows mixing to take place over time to
mimic small scale procedure of drop-wise
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Credit where credit is due: Thank you!
Huge shoutout to Dr. Zhang & Dr. Dickson for your continued input and expertise!

The entire BSE faculty and staff for all your support!

To our peers for your willingness to lend support academically and professionally!

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