Comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies to target a model immunomodulator to the lymphatic system

SUMMARY The current study aims to use an oral lipophilic prodrug approach to promote the delivery of a model immunomodulator, mycophenolic acid (MPA) to the lymphatic system to facilitate enhanced uptake into lymphocytes. The project builds on recent studies demonstrating that targeted drug delivery to lymphocytes in the lymphatics may enhance immunomodulatory effects [1,2]. Two types of lipophilic prodrugs (Fig. 1), alkyl chain derivatives (octyl mycophenolate, C8E; octadecyl mycophenolate, C18E; and octadecyl mycophenolamide, C18AM) and a triglyceride mimetic prodrug (1,3dipalmitoyl-2-mycophenoloyl glyceride, DPMG) demonstrated a marked increase (up to 80 fold) in lymphatic transport and accumulation in lymphocytes via different physiological mechanisms.