Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) micelles for rapamycin delivery: in vitro characterization and biodistribution

J Pharm Sci. 2011 Jun;100(6):2418-29. doi: 10.1002/jps.22467. Epub 2011 Jan 24.


Our objective was to synthesize an amphiphilic diblock copolymer for micellar delivery of rapamycin. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-b-PBC) with different hydrophobic core lengths were synthesized from methoxy poly(ethylene glycol) and 2-methyl-2-benzoxycarbonyl-propylene carbonate through ring-opening polymerization using 1,8-diazabicycloundec-7-ene as a catalyst. The critical micelle concentration of PEG-b-PBC was around 10(-8) M and depends on the hydrophobic core length. Rapamycin was effectively incorporated into micelles and drug loading increased with increasing hydrophobic core length, with maximal drug loading of 10% (w/w, drug/polymer), drug loading efficiency of about 85%, and mean particle size of around 70 nm. The drug release profile was also dependent on the hydrophobic core length and the drug release from PEG(114) -b-PBC(30) micelles was the slowest. We also determined the toxicity of rapamycin micelles on insulinoma (INS-1E) β-cells and human islets. Encapsulation of rapamycin into PEG-b-PBC micelles reduced its toxicity. Biodistribution of rapamycin-loaded PEG-b-PBC micelles was determined after systemic administration into mice. Rapamycin-loaded PEG-b-PBC micelles showed little difference in pharmacokinetics and biodistribution characteristics in mice compared with rapamycin carrying nanosuspension. In conclusion, rapamycin formulated with PEG-b-PBC micelles showed significantly reduced toxicity on INS-1E β-cells and human islets, but had similar biodistribution profiles as those of nanosuspensions.

Publication types

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

MeSH terms

  • Animals
  • Calorimetry, Differential Scanning
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / chemistry
  • Drug Stability
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / toxicity
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Mice
  • Micelles
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Particle Size
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / chemistry
  • Polypropylenes / chemical synthesis*
  • Polypropylenes / chemistry
  • Rats
  • Sirolimus / administration & dosage*
  • Sirolimus / chemistry
  • Sirolimus / pharmacokinetics*
  • Sirolimus / toxicity
  • Solubility
  • Surface Properties
  • Surface-Active Agents / chemical synthesis*
  • Surface-Active Agents / chemistry
  • Tissue Distribution


  • Drug Carriers
  • Immunosuppressive Agents
  • Micelles
  • Polypropylenes
  • Surface-Active Agents
  • poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate)
  • Polyethylene Glycols
  • Sirolimus