AUTHOR=Feturi Firuz G. , Weinstock Matthias , Zhao Wenchen , Zhang Wei , Schnider Jonas T. , Erbas Vasil E. , Oksuz Sinan , Plock Jan A. , Rohan Lisa , Spiess Alexander M. , Ferreira Lydia M. , Solari Mario G. , Venkataramanan Raman , Gorantla Vijay S. TITLE=Mycophenolic Acid for Topical Immunosuppression in Vascularized Composite Allotransplantation: Optimizing Formulation and Preliminary Evaluation of Bioavailability and Pharmacokinetics JOURNAL=Frontiers in Surgery VOLUME=5 YEAR=2018 URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2018.00020 DOI=10.3389/fsurg.2018.00020 ISSN=2296-875X ABSTRACT=
Mycophenolic acid (MPA), is the active form of the ester prodrug mycophenolate mofetil (MMF). MMF is an FDA approved immunosuppressive drug that has been successfully used in systemic therapy in combination with other agents for the prevention of acute rejection (AR) following solid organ transplantation (SOT) as well as in vascularized composite allotransplantation (VCA). Systemic use of MMF is associated with gastrointestinal adverse effects. Topical delivery of the prodrug could thus provide graft-targeted immunosuppression while minimizing systemic drug exposure. Our goal was to develop a topical formulation of MPA with optimal
Permeation studies were performed with a solution of MPA (10 mg/ml).
MPA in solution exhibited a steady state flux (3.8 ± 0.1 µg/cm2/h) and permeability (1.1 × 10−7 ± 3.2 × 10−9 cm/s). MPA in Lipoderm exhibited a steady state flux of 1.12 ± 0.24 µg/cm2/h, and permeability of 6.2 × 10−09 ± 1.3 × 10−9 cm/s across the biomimetic membrane. The cumulative release of MPA from Lipoderm, showed a linear single-phase profile with a R2 of 0.969.
We successfully developed for the first time, a topical formulation of MPA in Lipoderm with optimal