Skip to Main Content
 

Global Search Box

 
 
 
 

ETD Abstract Container

Abstract Header

Affinity-Based Drug Delivery Devices and its Applications in the Modulation of Cellular Processes

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Alteration of cell behavior is at the core of pathological diseases and design of drug delivery systems. Among those behaviors are cell morphogenesis, engraftment and migration. I have investigated how implantable polymer matrices can be engineered to treat different diseases using these cell behaviors as targets. Doing so have taken me to synthesize polymers containing different affinity binding ligands for the delivery of molecules of different sizes at the time scales needed in vivo. To meet these different cellular demands we have made use of the strength of binding between the drug or biomolecule to be delivered and the polymer. By using strong non-covalent interactions between molecules we can increase the total amount of drug loaded into the polymer matrix, modulate its release from the device and present this molecules in a local scenario. We have not only engineered the release rate of these polymers but also analyzed and evaluated their performance in vitro. Using surface plasmon resonance to determine the association constant of the host-guest complexes that form inside the polymer we have been able to predict which molecule pair will make good affinity guest and hosts. This characterization method has correlated well with the capacity of our affinity polymers to slow the delivery of a diverse set of molecules. To test the activity of the drugs loaded into these polymers we have made use of different longitudinal in vitro cell migration assays. This workflow of strength of binding prediction, polymer synthesis and in vitro testing has found applications in a variety of settings from cancer treatment to regenerative medicine. For cancer treatment we have evaluated the release of small (MW< 500) anti-angiogenic molecules to slowly release over time. When implanted into animals this slow releasing polymers delay the growth of a glioblastoma tumors in a mouse animal model. Using the same principles we have also engineered polymers capable of releasing the stem cell recruiting cytokine, CCL7, for a period of several weeks. We have confirmed this cytokine to be bioactive throughout the period of release at the site of polymer implantation. The net result is an increased retention of therapeutic mesenchymal cells in the site of injury. This platform has potential as an implantable medical device to treat urinary incontinence or other medical applications where stem cell retention is needed. These different affinity polymers allow for the bioactive release of molecules at the timescales and concentrations needed with noticeable effects in medically relevant models of cancer and regenerative medicine. As the system moves into the future we see the platform developing into different device scales and geometries and the addition of environmentally mediated interactions between the polymer and the cells involved in the progression of the diseases.
Horst von Recum (Advisor)
Adonis Hijaz (Committee Member)
Agata Exner (Committee Member)
Zheng-Rong Lu (Committee Member)
126 p.

Recommended Citations

Citations

  • Rivera, E. (2014). Affinity-Based Drug Delivery Devices and its Applications in the Modulation of Cellular Processes [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1417792663

    APA Style (7th edition)

  • Rivera, Edgardo. Affinity-Based Drug Delivery Devices and its Applications in the Modulation of Cellular Processes. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1417792663.

    MLA Style (8th edition)

  • Rivera, Edgardo. "Affinity-Based Drug Delivery Devices and its Applications in the Modulation of Cellular Processes." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1417792663

    Chicago Manual of Style (17th edition)