Transdermal delivery of peptide hormones to treat tibial bone stress fractures using DiffusiMax liposomal cream base
The goal of this Mitacs research proposal study is to develop and apply experimental methodology for transdermal delivery of bone-targeting peptide hormone drugs. We aim to deliver these compounds using an appropriate hydrophilic-hydrophobic Diffusimax liposomal drug delivery cream base to anatomically superficial bone, at the sites of stress fractures (also known as shin-splints) in order to trigger bone repair, reduce pain burden, and to minimize possible side effects if those drugs were used systemically. In order to achieve those endpoints, the trainees will initially measure the permeability of the peptide hormones Calcitonin or PTH (and bone-targeting variants) in the lab using artificial membranes and animal skin tissue, with acetate (pH 5) and phosphate (pH 7.4) buffers as receiving medium when applied as liposomal cream preparations. We will then conduct in vivo studies using an animal model of tibial stress fracture, and evaluate plasma and bone concentrations of Calcitonin or PTH, and use histology to gauge the success of bone repair. The general hypothesis is that: the transdermal delivery of Calcitonin, PTH or bone-targeting variants will improve local bone availability of the peptide hormone, especially when applied to treat tibial shin-splints.