Distribution of therapeutic proteins into thoracic lymph after intravenous administration is protein size-dependent and primarily occurs within the liver and mesentery

Journal of Controlled Release : Official Journal of the Controlled Release Society
Preeti YadavNatalie L Trevaskis

Abstract

Therapeutic proteins can facilitate the targeting and treatment of lymphatic diseases (such as cancer metastases, infections and inflammatory diseases) since they are cleared via the lymphatics following interstitial (SC or IM) administration. However, therapeutic proteins are often administered intravenously (IV). Recently therapeutic proteins have been found to access the thoracic lymph in surprisingly high quantities after IV administration. The aim of this study was to determine, for the first time, the major sites of thoracic lymph access of therapeutic proteins, and the protein properties that enhance lymph access, after IV administration. In order to achieve this, novel methods were developed or optimized to collect hepatic, mesenteric or thoracic lymph from male SD rats. Four different sized PEGylated or non-PEGylated therapeutic proteins (native interferon α2b (IFN, 19kDa), PEGylated interferon α2b (IFN-PEG12, 31kDa), PEGylated interferon α2a (IFN-PEG40, 60kDa) or trastuzumab (150kDa)) were then administered via short IV infusion, and plasma and lymph concentrations of the proteins determined via ELISA. The recovery of the therapeutic proteins in the thoracic lymph duct, which collects lymph from most of the body, was ...Continue Reading

Citations

Jul 17, 2020·Frontiers in Physiology·Natalie L TrevaskisChristopher J H Porter
Feb 19, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Gracia GraciaNatalie L Trevaskis
Aug 29, 2021·Pharmaceutics·Nolwenn TessierCatherine Martel
Sep 17, 2021·Journal of Crohn's & Colitis·Roger SuauJosep Manyé

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