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

19 Citations (Scopus)

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 - Jan 1 2011

Fingerprint

Micelles
Sirolimus
Islets of Langerhans
Pharmaceutical Preparations
Insulinoma
Ethylene Glycol
In Vitro Techniques
poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate)
Particle Size
Polymerization
Polymers
Pharmacokinetics

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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title = "Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) micelles for rapamycin delivery: In vitro characterization and biodistribution",
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.",
keywords = "Biodistribution, Micelles, Nanosuspensions, Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate), Rapamycin",
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T1 - Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) micelles for rapamycin delivery

T2 - In vitro characterization and biodistribution

AU - Lu, Wenli

AU - Li, Feng

AU - Mahato, Ram I

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

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KW - Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate)

KW - Rapamycin

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JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

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