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

Wenli Lu, Feng Li, Ram I. Mahato

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 PEG114-b-PBC30 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.

Original languageEnglish (US)
Pages (from-to)2418-2429
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number6
DOIs
StatePublished - Jun 2011

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Keywords

  • Biodistribution
  • Micelles
  • Nanosuspensions
  • Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate)
  • Rapamycin

ASJC Scopus subject areas

  • Pharmaceutical Science

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