Film- and ointment-based delivery systems for the transdermal delivery of TNP-470

Eva Abramov, Ouri Schwob, Ofra Benny*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Pathological angiogenesis, the process of new blood vessel formation, is responsible for a broad range of neovascular-related systemic diseases. One of the first antiangiogenic compounds tested in clinical trials against cancer was TNP-470. Despite promising activity the injectable drug showed poor plasma stability and caused adverse side effects in high doses lead to termination of the trials. In our current work, we introduce the development of a transdermal delivery systems for controlled release of TNP-470. Such formulation can potentially reduce toxicity due to controlled continuous dosing and improve stability by avoiding gastrointestinal first pass metabolism. Although transdermal delivery is a very challenging route for drug administration due to the low permeability of the skin, here we present a successful development of two different drug delivery systems, film and ointment for dermal application of TNP-470. Chitosan film had high loading capacity of up to 50% w/w of TNP-470 compared with 10% maximum loading in hydrocarbon ointment. A detailed step-by-step development of TNP-470 films, from the initial solvent screening to final optimized formulation, is presented. Ex vivo skin permeation studies demonstrated a superior release of the drug from the film formulation compared with the ointment. Furthermore, histological test of the skin confirmed ointment safety showing no evidence of skin tissues damage. Our results present novel, promising, controlled release drug delivery systems with improved stability, efficacy, and safety profile of TNP-470 via transdermal route.

Original languageAmerican English
Pages (from-to)2586-2595
Number of pages10
JournalPolymers for Advanced Technologies
Issue number10
StatePublished - 1 Oct 2019

Bibliographical note

Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.


  • antiangiogenic drug
  • chitosan film
  • ointment
  • transdermal delivery


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