Drug delivery to osteoclast receptor targets

  • Author / Creator
    Kalvapalle, Rohit
  • Osteoporosis is a skeletal disorder that affects millions of people worldwide, and is characterized by the accelerated loss of bone mass. Current anti-resorptive drug approaches such as bisphosphonates and salmon calcitonin exhibit severe side effects and very low bioavailability, respectively. In this study, we have designed, synthesized, and performed preliminary tests on a novel conjugate that targets the RANK receptor on bone resorbing cells (osteoclasts) in vitro with one arm, while delivering a specific effector molecule, calcitonin, to osteoclasts with the other arm. First, we successfully generated osteoclasts from precursor RAW 264.7 cells and confirmed that they were functional. We also designed a resorption assay that can be used to test the efficacy of new and existing anti-resorptive drugs. RAW 264.7 cells were then treated with an antibody to RANK to prove that anti-RANK could be used as a targeting mechanism. We then showed that delivery of calcitonin-loaded anti-Calcitonin antibodies onto osteoclasts results in the association of calcitonin onto its receptors on osteoclasts. Finally, we constructed a novel conjugate: calcitonin–Streptavidin–anti-RANK, and showed that it can be used to introduce calcitonin into an osteoclast-like microenvironment.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Faculty of Pharmacy and Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
    • Doschak, Michael (Pharmacy and Pharmaceutical Sciences)
  • Examining committee members and their departments
    • Kane, Kevin (Medical Microbiology and Immunology)
    • Suresh, Mavanur (Pharmacy and Pharmaceutical Sciences)
    • Matyas, John (Cell Biology and Anatomy, University of Calgary)