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Liposome-mediated Delivery of the p21 Activated kinase-1 (PAK-1) Inhibitor IPA-3 Limits Prostate Tumor Growth in Vivo

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

Nanomedicine. 2016 Jul;12(5):1231-1239.

PMID: 26949163

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 139nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of -28.1, neither of which changed over 14days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2day/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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP42521824	IPA-3		42521-82-4	Price

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