|MIT Department: Chemical Engineering
Faculty Mentor: Prof. Paula Hammond
Undergraduate Institution: Spelman College
I am a rising junior Chemistry major in the Dual Degree Engineering Program with a concentration in Biomedical Engineering at Spelman College. My research interest includes biomaterial development and pharmaceutical engineering. I plan to pursue a Ph.D. in Biomedical Engineering and focus on pediatric diseases and disorders research. Outside of the classroom, I enjoy traveling, journaling, running, and exploring new things.
Manipulating PEGylated PAMAM Dendrimers and Comparing Cartilage and Meniscus Partitioning to Increase the Efficacy of
Post Traumatic Osteoarthritis Treatment
Laila N.J. Hayes1, Brandon M. Johnston2,3, and Paula T. Hammond2,3
1Department of Chemistry and Dual Degree Engineering, Spelman College
2Koch Institute for Integrative Cancer Research,
Massachusetts Institute of Technology
3Department of Chemical Engineering, Massachusetts Institute of Technology
Osteoarthritis (OA) is a painful disease that affects up to 30 million people each year. This disease manifests as the degradation of articular cartilage and ultimately leading to the exposure of underlying bone. Potential disease-modifying OA treatments have been studied; however, these locally injected biologics require a drug delivery system to increase joint residence time and therapeutic efficacy. Previous studies have shown that cationic polyamidoamine (PAMAM) dendrimers covalently modified with polyethylene glycol (PEG) can adhere to the densely anionic aggrecan chains of articular cartilage through electrostatic interactions and improve the efficacy of covalently-bound therapies. Meniscus tissue is capable of electrostatic interactions with the cationic dendrimer as well, which reduces the amount of dendrimer-bound therapy uptaken by the target tissue. This research evaluates the partitioning of PEG-PAMAM conjugates into cartilage and meniscus using an ex vivo bovine model. By testing a small library of conjugates, we can identify the most effective PEG chain length and chain density in order to achieve effective accumulation in cartilage. This research used proton nuclear magnetic resonance spectroscopy (1H-NMR) and ex vivo tissue in a salt-based assay to characterize the PEG-PAMAM conjugates and an ex vivo, co-uptake experiment examining dendrimer uptake into cartilage and meniscus simultaneously to better simulate partitioning in the joint. For all the conjugates tested, articular cartilage has a higher uptake percentage than meniscus. This difference in uptake, or partitioning, is more significant for PEG with 4 repeat units (PEG 4) than PEG 40 for all grafting densities tested. For both chain lengths, however, higher chain densities resulted in greater partitioning than lower chain densities. Thus, these findings suggest that a shorter PEG chain and greater PEG density results in more significant partitioning into cartilage. Based on this information, we can improve the efficacy of dendrimer-bound therapies by controlling conjugate trafficking in the joint.