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

Journal: Nanomedicine : nanotechnology, biology, and medicine 2017;12(5):1231-1239

PMID: 26949163

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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.

Address: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical center, Augusta, GA.; Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan.; Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA.; Interdisciplinary Toxicology Program, University of Georgia, Augusta, AG.; Department of Medicine, Vascular Biology Center and Cancer Center, Georgia Regents University, Augusta, GA.

DOI: 10.1016/j.nano.2016.01.003