(7dw) Optimizing Polymeric Nanoparticle Synthesis for Drug Delivery Using Experimental Design

Degree expected May 2018

Research Interests:

Nanotechnology has shown much promise in the medical field in terms of diagnostics, therapeutics, and imaging. Nanoparticles, in particular, provide a multimodal platform that can be easily tailored depending on the characteristics of the disease. Modifications include size, shape, material composition, drug payload, and targeting moieties. For clinical trials and eventual FDA approval, nanoparticles must be consistent in biological behavior and pharmacological profile. Unfortunately, nanoparticles are typically produced in small, non-homogenous batches, which leads to difficulty in experimental reproducibility and scale up for commercial production. Nanoprecipitation, a nanoparticle synthesis method, can be operator independent, scalable, and due to the short characteristic mixing time, used to encapsulate hydrophobic drugs in particles with a narrow size distribution. Work has been done to determine what factors, particularly what process parameters, impact particle characteristics. Little work, however, has been done on the molecular level to show the effect polymer chemistry as well as drug class has on particle characteristics, encapsulation efficiency, and drug release profile. Certainly, these variables, process and molecular, have not been combined to predict desired outcomes. As such, my research aims to show and optimize the factors that most affect particle size, polydispersity, drug encapsulation efficiency, and drug release profile using an industrial useful method such as nanoprecipitation and a combination of response surface experimental design and molecular modeling.

PhD Dissertation: “Nanoparticle Synthesis for the Treatment of Lung Cancer”

Under supervision of Dr. Timothy M. Brenza, Chemical and Biological Engineering, South Dakota School of Mines & Technology

MS Project: “Cross-linked Nanoassemblies for Tumor-Targeted Drug Delivery”

Under supervision of Dr. Younsoo Bae, Pharmaceutical Sciences, University of Kentucky

Research Experience:

Over the course of my academic career I have worked on several different research projects within the Chemical and Biological Engineering and Pharmaceutical Sciences realm, which have ranged from “Cross-linked Nanoassemblies for Tumor-Targeted Drug Delivery” to “Anaerobic Digestion of Cardboard and Paper Waste” back to “Nanoparticle Synthesis for the Treatment of Lung Cancer”. This has led to significant experience with design of experiments as well as many analytical techniques and instrumentation including differential scanning calorimetry (DSC), dynamic light scattering (DLS), fast protein liquid chromatography (FPLC), fluorescence microscopy, gas chromatography (GC), gel permeation chromatography (GPC), high-performance liquid chromatography (HPLC), mammalian cell culture, scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV/Vis spectroscopy, and Western blotting.

Teaching Interests and Experience:

I have been a Graduate Teaching Assistant for several undergraduate lecture and laboratory courses in Chemical Engineering at South Dakota School of Mines & Technology of which duties included grading, proctoring, and guest lecturing. I was also the instructor of record for one semester of Chemical Engineering Fluids Laboratory. In addition to my formal teaching experience, I have spent considerable time mentoring undergraduate and other graduate students within the lab group and for two summers as part of the University of Kentucky’s Engineered Bioactive Interfaces and Devices NSF REU.

Though engineering courses still benefit from the standard lecture and homework method, a method I plan on using often, I believe students learn more about the subject and how to collaborate with each other through projects and discussion. Projects also help foster creativity and interest in the subject when students are allowed to select their own topic. I am interested in teaching courses such as material balances, fluid dynamics, and mass transfer as well as electives such as statistics/experimental design, drug delivery, and bionanotechnology.

Future Direction:

In the United States, the likelihood of being diagnosed with some form of cancer with one’s lifetime is 1 in 2 for men and 1 in 3 for women. For lung cancer, in particular, the incidence rate is 1 in 14 for men and 1 in 17 for women with the overall five-year survival rate a mere 18.0 percent. The standard chemotherapeutic treatment of lung cancer, which involves a “cocktail” of steroids and several anticancer drugs, is physically demanding for the patient and requires a trained professional administer the dose. As such, an inhalable nanoparticle formula, which combines two or more anticancer agents, would be beneficial. As faculty, I would like to continue my optimization of nanoparticle synthesis work in pursuit of this goal. First, the current model equation used for predicting nanoparticle size would need to be expanded to account for different classes of polymers as the selected polymer dictates the degradation rate and release profile of the drug. Second, this model equation would also need to account for various added complexities such as more than one polymer, more than one drug, and any targeting moieties. While most current FDA-approved nanomedicines involve just one drug encapsulated in one polymer, the drug delivery field is becoming more intricate and personalized. This work could also be expanded to other types of cancer as well as other diseases.

My academic training has prepared me well for this challenge of connecting successful in vivo results to an industrially beneficial and marketable product. First, I have been classically educated as a chemical engineer with firsthand industrial process engineering experience in a fermentation and ethanol production facility. Second, I have elected to take courses in a variety of topics including experimental design, polymers, wastewater treatment, bioseparations, pharmacokinetics, biochemistry, and cancer biology. Third, I have participated in several entrepreneurial programs such as South Dakota School of Mines’ Engineers Make Great Entrepreneurs and Harvard Business School’s Credential of Readiness (CORe).

Selected Publications:

1. Asato, C.M., et al., Batch anaerobic digestion of synthetic military base food waste and cardboard mixtures. Bioresour Technol, 2016. 216: p. 894-903.

2. Gonzalez-Estrella, J., et al., Effect of structural carbohydrates and lignin content on the anaerobic digestion of paper and paper board materials by anaerobic granular sludge. Biotechnol Bioeng, 2017. 114(5): p. 951-960.