Analytical Method for Transdermal Delivery of the Anti-angiogenic Compound TNP-470
Eva Abramov, Ouri Schwob and Ofra Benny*
The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- *Corresponding Author:
- Ofra Benny
Institute for Drug Research, The School of Pharmacy, Faculty of Medicine
Campus Ein Karem, The Hebrew University, Jerusalem 91120, Israel
E-mail: [email protected]
Received date: May 06, 2017; Accepted date: May 19, 2017; Published date: May 24, 2017
Citation: Abramov E, Schwob O, Benny O (2017) Analytical Method for Transdermal Delivery of the Antiangiogenic Compound TNP-470. J Anal Bioanal Tech 8:365. doi:10.4172/2155-9872.1000365
Copyright: © 2017 Abramov E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Pathological angiogenesis is a critical component in cancer, in chronic systemic inflammatory diseases such as psoriasis and rheumatoid arthritis, and in ocular diseases. Anti-angiogenic drugs have the ability to prevent, inhibit, and regress newly formed blood vessels. The activity of TNP-470 (chloro acetylcarbamoylfumagillol), a potent anti-angiogenic drug, has been demonstrated in numerous preclinical studies and in eight clinical studies involving more than three hundred patients. Despite its encouraging efficacy, TNP-470 is unstable compound with short plasma half-life, and, as was found clinically it can cause neurotoxicity side-effects at high doses. In light of these limitations, developing a transdermal drug delivery for TNP-470, can offer a novel and promising clinical usage for this drug by improving its bioavailability, controlled dosage and safety profile. In this work, we developed a reliable method for skin permeation studies of TNP-470, using the pig skin in Franz diffusion cells and High-Performance Liquid Chromatography (HPLC) analysis. Additionally, we performed a broad stability and degradation studies of TNP-470 in different mediums and identify optimal stabilizing conditions in acetate buffer pH-4.5, which can be used for transdermal formulation. Our results demonstrated excellent permeability properties of TNP-470 through the pig skin, where 25% from the initial amount was crossed through the skin membrane after 72 hours. Our results suggesting that TNP-470 is a good candidate for transdermal drug delivery, whereas, an optimal dermal formulation would improve drug’s pharmacokinetic properties and toxicity profile by introducing it in a slow release system.