Industrial Scale Reactor for Paclitaxel-loaded

PLGA Nanoparticles
Sara Peterson, Sarah Chaikind, Stephanie Lundgren, Emily Gee
Faculty Advisor: Dr. Mike Zhang

Introduction Engineering Considerations

Problem Statement
Breast cancer is expected to affect 250,000 new cases in 2017. The
current treatment option, chemotherapy, involves adverse side effects.
Proposed Solution
Create a reactor that produces drug-loaded nanoparticles on a large
scale to treat breast cancer while bypassing side effects
Utilize Paclitaxel, a lipid soluble breast cancer drug, and poly(lactic-co-
glycolic acid), a biodegradable, FDA approved nanoparticle for drug
production
Figure 1. Image courtesy of Womens Health
Main Criteria
One year run time under $12B
Production of PLGA nanoparticles between 160 nm and 170 nm in diameter
PLGA loaded with Paclitaxel at 80% encapsulation efficiency
Main Constraints
Scale up difficulties associated with nanoparticle production
Very high target population size 18 systems needed to service United States patients
Maintenance of nanoparticles through process to ensure correct size and drug loading of each particle to meet FDA requirements
Standards
FDA Title 21, 600 series, 800 series covering biological vaccines and medical products
National Institutes of Standards and Technology: nanoparticle measurements and standards for use in biomedical applications & health
Membrane Bioreactors: 89.1-89.9 (e.g. Pretreatment, Tank Design, Tank Arrangement, Mixing Equipment, Disinfection, etc.)

Drug Loading Process Three Reactor Design and Inventor Drawings

Figure 3.1 Figure 3.2 Figure 3.3 Figure 3.4 Figure 3.5 Figure 3.6 Figure 3.7 Figure 3.8

3.1.Three part reactor design, 3D image 3.2. Three part reactor 3.3. Organic Phase 3.4. Impeller for 3.5. Aqueous phase 3.6. Mixing reactor, part drawing 3.7. Impeller for 5000 L 3.8. Divider between
interconnected with pipes design, part drawing reactor, part drawing Organic and reactor, part drawing 1. Thermocouple mixing tank reactor. organic and aqueous
1. 500 L Organic phase 1. Thermocouple Aqueous reactors 1. Thermocouple 2. Inlet from organic reactor Flat, curved blades phases in 5000 L mixing
Reynolds Number for Reactors reactor 2. Impeller mounted with agitators 2. Offset impeller 3. Phase divider between organic maximize shear stress tank. Nine holes allow
Organic: 9.80 x 105 2. 4000 L Aqueous phase 15 from vertical and oriented 45 3. Outlet to mixing and aqueous phase (10.04 L/hr) during mixing to for even flow at 10.04 L/
Aqueous: 1.38 x 105 reactor offset from center relative to reactor 4. Inlet from aqueous reactor homogenize hr for a total mixing
Mixing: 7.13 x 104 3. 5000 L Mixing Reactor 3. Outlet to mixing 5. Outlet to vacuum nanoparticle production time of 36 hours.
Figure 2. Drug loading process specifications
reactor 6. Bottom mounted impellar size

SuperPro Representation of Industrial Process Sample Calculations Cost Analysis of Design

References
Acknowledgements
Thank you so much to our faculty advisor, Dr. Mike
Zhang, our external advisor, Dr. Matt Dickson, the
Biological Systems Engineering Department, and the
BSE Class of 2017 for all of the encouragement and
support throughout this project. Go Hokies!