title: Liposome-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitor IPA-3 limits prostate tumor growth in vivo.
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.
authors.affiliation: 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.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Azayzih
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA.
authors.forename: Wided N
authors.initials: WN
authors.lastname: Missaoui
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA.|Interdisciplinary Toxicology Program, University of Georgia, Augusta, AG.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Cummings
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical center, Augusta, GA.|Department of Medicine, Vascular Biology Center and Cancer Center, Georgia Regents University, Augusta, GA.
authors.forename: Payaningal R
authors.initials: PR
authors.lastname: Somanath
mesh_terms: D004220:Disulfides / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes; D008297:Male; D009284:Naphthols / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: D004220:Disulfides; C541795:IPA-3 compound; D008081:Liposomes; D009284:Naphthols; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: IPA-3; Liposomes; PAK-1; Prostate cancer