title: Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines.
abstract: The phosphoinositide-3-kinases (PI3Ks) are a conserved family of lipid kinases that phosphorylate the 3-hydroxyl group of phosphatidylinositols in response to extracellular stimuli. PI3K pathway is enrolled in different kinds of human cancer and plays a prominent role in cancer cell growth and survival. Several PI3K inhibitors have been recently identified but some PI3K inhibitors with high potency in vitro do not show satisfactory effects in animal cancer models because of the poor pharmaceutical properties in vivo such as poor solubility, instability, and fast plasma clearance rate. In this study, we developed a sustained release system of PI3K inhibitor (TGX221) based on polyhydroxyalkanoate nanoparticles (NP) and used it to block proliferation of cancer cell lines. TGX221 was gradually released from PHA-based NP and growth of cancer cell lines was significantly slower in NP-TGX221-treated cells than in either negative controls or in cells receiving free TGX221. Since poor bioavailability and limited in vivo half-life are common features of hydrophobic PI3K inhibitors, our results open the way to similar formulation of other PI3K blockers and to new strategies in cancer treatment.
authors.affiliation: Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, People's Republic of China. luxy05@mail.xjtu.edu.cn
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Lu
authors.forename: Elisa
authors.initials: E
authors.lastname: Ciraolo
authors.forename: Rachele
authors.initials: R
authors.lastname: Stefenia
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054813:Polyhydroxyalkanoates / Q000737:chemistry*; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054813:Polyhydroxyalkanoates; D011744:Pyrimidinones; C504718:TGX 221