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 language | English |
|---|---|
| Pages (from-to) | 1231-1239 |
| Number of pages | 9 |
| Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jul 1 2016 |
| Externally published | Yes |
Keywords
- IPA-3
- Liposomes
- PAK-1
- Prostate cancer
ASJC Scopus subject areas
- Bioengineering
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- Materials Science(all)
- Pharmaceutical Science