title: Sterically stabilized liposomes incorporating the novel anticancer agent phospho-ibuprofen (MDC-917): preparation, characterization, and in vitro/in vivo evaluation.
abstract: OBJECTIVE
  To incorporate phospho-ibuprofen (P-I), a lipophilic, water insoluble novel anti-cancer agent, into pegylated liposomes and upon formulation optimization to evaluate its antitumor activity in vitro and in vivo.
  
  
  METHODS
  P-I loaded liposomes were prepared using the thin-film hydration method, and characterized for size, zeta potential, drug content and drug release. We examined their physical stability by particle size changes; their lyophilization ability in the presence of cryoprotectants; and their antitumor activity in vitro in human cancer cell lines and in vivo in a xenograft murine model.
  
  
  RESULTS
  P-I was successfully loaded into liposomes consisting of soy-PC and PEG(2000)-PE. These liposomes were <150 nm in diameter; exhibited prolonged stability in suspension and can be lyophilized using sucrose as cryoprotectant. P-I liposomes inhibited the growth of human cancer cell lines in vitro and in vivo of xenograft in nude mice to a greater extent than free P-I.
  
  
  CONCLUSIONS
  High levels of P-I can be incorporated into liposomes which can be lyophilized in the presence of sucrose and showed good stability upon storage. Moreover, these drug-incorporating liposomes were capable of inhibiting the growth of xenografted tumors in mice more effectively than free P-I. These results justify further development of the P-I liposomes.
authors.affiliation: Division of Cancer Prevention, Department of Medicine, Stony Brook University Stony Brook, Stony Brook, New York 11794-8173, USA.
authors.forename: George
authors.initials: G
authors.lastname: Mattheolabakis
authors.forename: Ting
authors.initials: T
authors.lastname: Nie
authors.forename: Panayiotis P
authors.initials: PP
authors.lastname: Constantinides
authors.forename: Basil
authors.initials: B
authors.lastname: Rigas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003451:Cryoprotective Agents / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D005612:Freeze Drying; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D010755:Organophosphates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C559491:2-(4-isobutylphenyl)propionic acid 4-(diethoxyphosphoryloxy)butyl ester; D000970:Antineoplastic Agents; D003451:Cryoprotective Agents; D008055:Lipids; D008081:Liposomes; D010755:Organophosphates; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D007052:Ibuprofen
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