Liposome-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitor IPA-3 limits prostate tumor growth in vivo

Ahmad Al-Azayzih, Wided N. Missaoui, Brian S. Cummings, Payaningal R. Somanath

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

P21 activated kinases-1 (PAK-1) is implicated in various diseases. It is inhibited by the small molecule 'inhibitor targeting PAK1 activation-3' (IPA-3), which is highly specific but metabolically unstable. To address this limitation we encapsulated IPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of -. 28.1, neither of which changed over 14 days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7 days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2 day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulation for the treatment of prostate cancer.

Original languageEnglish
Pages (from-to)1231-1239
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number5
DOIs
Publication statusPublished - Jul 1 2016
Externally publishedYes

Keywords

  • IPA-3
  • Liposomes
  • PAK-1
  • Prostate cancer

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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