Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biologicalmacromolecules

Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of
pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site
into the circulation, poses a particular problem. Here we will explore how recombinant hyaluronidase, an
enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote
absorption into the draining blood and lymph capillaries. We will also explore the downstream effects of
hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph
node structure and promote drug penetration into the lymph node mass. This has significant potential for
improved drug targeting.