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Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines.

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 survi... Full description

Journal Title: Applied microbiology and biotechnology March 2011, Vol.89(5), pp.1423-1433
Main Author: Lu, Xiao-Yun
Other Authors: Ciraolo, Elisa , Stefenia, Rachele , Chen, Guo-Qiang , Zhang, Yali , Hirsch, Emilio
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1432-0614 ; DOI: 10.1007/s00253-011-3101-1
Link: http://search.proquest.com/docview/851476197/?pq-origsite=primo
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recordid: proquest851476197
title: Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines.
format: Article
creator:
  • Lu, Xiao-Yun
  • Ciraolo, Elisa
  • Stefenia, Rachele
  • Chen, Guo-Qiang
  • Zhang, Yali
  • Hirsch, Emilio
subjects:
  • Animals–Drug Effects
  • Cell Line, Tumor–Chemistry
  • Cell Proliferation–Pharmacokinetics
  • Drug Carriers–Pharmacology
  • Enzyme Inhibitors–Pharmacokinetics
  • Humans–Pharmacology
  • Morpholines–Chemistry
  • Nanoparticles–Antagonists & Inhibitors
  • Phosphatidylinositol 3-Kinases–Chemistry
  • Polyhydroxyalkanoates–Pharmacokinetics
  • Pyrimidinones–Pharmacology
  • Drug Carriers
  • Enzyme Inhibitors
  • Morpholines
  • Polyhydroxyalkanoates
  • Pyrimidinones
  • Tgx 221
  • Phosphatidylinositol 3-Kinases
ispartof: Applied microbiology and biotechnology, March 2011, Vol.89(5), pp.1423-1433
description: 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. ; Includes references ; p. 1423-1433.
language: eng
source:
identifier: E-ISSN: 1432-0614 ; DOI: 10.1007/s00253-011-3101-1
fulltext: fulltext
issn:
  • 14320614
  • 1432-0614
url: Link


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titleSustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines.
creatorLu, Xiao-Yun ; Ciraolo, Elisa ; Stefenia, Rachele ; Chen, Guo-Qiang ; Zhang, Yali ; Hirsch, Emilio
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ispartofApplied microbiology and biotechnology, March 2011, Vol.89(5), pp.1423-1433
identifierE-ISSN: 1432-0614 ; DOI: 10.1007/s00253-011-3101-1
subjectAnimals–Drug Effects ; Cell Line, Tumor–Chemistry ; Cell Proliferation–Pharmacokinetics ; Drug Carriers–Pharmacology ; Enzyme Inhibitors–Pharmacokinetics ; Humans–Pharmacology ; Morpholines–Chemistry ; Nanoparticles–Antagonists & Inhibitors ; Phosphatidylinositol 3-Kinases–Chemistry ; Polyhydroxyalkanoates–Pharmacokinetics ; Pyrimidinones–Pharmacology ; Drug Carriers ; Enzyme Inhibitors ; Morpholines ; Polyhydroxyalkanoates ; Pyrimidinones ; Tgx 221 ; Phosphatidylinositol 3-Kinases
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descriptionThe 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. ; Includes references ; p. 1423-1433.
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