MIT Department: Chemical Engineering
Undergraduate Institution: University of Kansas
Faculty Mentor: Paula Hammond
Research Supervisor: John Martin
My name is Nicole Montoya and I am from San José, Costa Rica. I am a rising senior studying Chemical Engineering at the University of Kansas. My main research interest is the study of different methods of drug delivery. I enjoy reading, traveling and meeting new people.
2018 Research Abstract
On-demand delivery of antioxidants from layer-by-layer films specifically in response to high levels of oxidative stress
Nicole Montoya1, John Martin2 and Paula Hammond2
1Department of Chemical Engineering, University of Kansas
2Department of Chemical Engineering, Massachusetts Institute of Technology
For non-healing, critically sized bone defects, reactive oxygen species (ROS) have been implicated as a factor contributing to the lack of bone regeneration. High levels of oxidative stress also inhibit bone integration with titanium implants, specifically in hips and femurs. Previous work has demonstrated increased bone healing after systemic antioxidant treatment, though this strategy cannot respond to local fluctuations in ROS levels at the defect site. Therefore, we have designed materials coated with an ROS-responsive drug delivery system that specifically releases an antioxidant drug in high concentrations of ROS, thus prolonging the localized antioxidant delivery window. The drug-containing coating is constructed using layer-by-layer (LbL) assembly of cationic, ROS-degradable poly(thioketal β-amino amide) (PTK-BAA) and anionic, drug-sequestering poly(cyclodextrin) (polyCD) polymers. We first demonstrated through profileometry studies that PTK-BAA and polyCD can effectively form LbL films with linear film thickness growth. We next loaded the naturally-derived, hydrophobic drug molecule curcumin into the hydrophobic domains of polyCD and determined a maximum drug loading of 25 µg curcumin/mg of polyCD. The total drug loading per bilayer was determined to be 800 ng/cm2, and the optimal number of bilayers for maximum release was 60 bilayers. Additionally, an in vitro release study of drug-coated implants showed greater curcumin release when treated with 1mM hydrogen peroxide versus those treated solely with PBS, indicating that the system is ROS responsive. In conclusion, we have successfully optimized this ROS-responsive antioxidant delivery system and hope to find positive results in future in vitro and in vivo studies.