Sterically stabilized liposomes incorporating the novel anticancer agent phospho-ibuprofen (MDC-917): preparation, characterization, and in vitro/in vivo evaluation

Pharm Res. 2012 Jun;29(6):1435-43. doi: 10.1007/s11095-011-0619-y. Epub 2011 Nov 10.

Abstract

Purpose: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Cryoprotective Agents / chemistry
  • Dose-Response Relationship, Drug
  • Drug Compounding
  • Drug Stability
  • Female
  • Freeze Drying
  • Humans
  • Ibuprofen / administration & dosage
  • Ibuprofen / analogs & derivatives*
  • Ibuprofen / chemistry
  • Ibuprofen / pharmacology
  • Inhibitory Concentration 50
  • Injections, Intraperitoneal
  • Kinetics
  • Lipids / chemistry*
  • Liposomes
  • Mice
  • Mice, SCID
  • Organophosphates / administration & dosage
  • Organophosphates / chemistry
  • Organophosphates / pharmacology*
  • Particle Size
  • Phosphatidylcholines / chemistry
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Solubility
  • Surface Properties
  • Technology, Pharmaceutical / methods
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • 2-(4-isobutylphenyl)propionic acid 4-(diethoxyphosphoryloxy)butyl ester
  • Antineoplastic Agents
  • Cryoprotective Agents
  • Lipids
  • Liposomes
  • Organophosphates
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Ibuprofen