PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release: Cyclosporin A as an example

Diana Velluto, Davide Demurtas, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Micelles formed from amphiphilic block copolymers have been explored in recent years as carriers for hydrophobic drugs. In an aqueous environment, the hydrophobic blocks form the core of the micelle, which can host lipophilic drugs, while the hydrophilic blocks form the corona or outer shell and stabilize the interface between the hydrophobic core and the external medium. In the present work, mesophase behavior and drug encapsulation were explored in the AB block copolymeric amphiphile composed of poly(ethylene glycol) (PEG) as a hydrophile and poly(propylene sulfide) PPS as a hydrophobe, using the immunosuppressive drug cyclosporin A (CsA) as an example of a highly hydrophobic drug. Block copolymers with a degree of polymerization of 44 on the PEG and of 10, 20 and 40 on the PPS respectively (abbreviated as PEG44-b-PPS10, PEG44-b-PPS20, PEG44-b-PPS40) were synthesized and characterized. Drug-loaded polymeric micelles were obtained by the cosolvent displacement method as well as the remarkably simple method of dispersing the warm polymer melt, with drug dissolved therein, in warm water. Effective drug solubility up to 2 mg/mL in aqueous media was facilitated by the PEG-b-PPS micelles, with loading levels up to 19% w/w being achieved. Release was burst-free and sustained over periods of 9-12 days. These micelles demonstrate interesting solubilization characteristics, due to the low glass transition temperature, highly hydrophobic nature, and good solvent properties of the PPS block.

Original languageEnglish
Pages (from-to)632-642
Number of pages11
JournalMolecular Pharmaceutics
Volume5
Issue number4
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Fingerprint

Cyclosporine
Micelles
Pharmaceutical Preparations
Drug Carriers
Ethylene Glycol
Transition Temperature
Immunosuppressive Agents
Drug Liberation
poly(ethylene glycol)-stabilized poly(propylene sulfide)
Polymerization
Solubility
Glass
Polymers
Water

Keywords

  • Block copolymer
  • Cyclosporin A
  • Nanoparticle
  • Poly(propylene sulfide)
  • Polymer micelle

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release : Cyclosporin A as an example. / Velluto, Diana; Demurtas, Davide; Hubbell, Jeffrey A.

In: Molecular Pharmaceutics, Vol. 5, No. 4, 01.07.2008, p. 632-642.

Research output: Contribution to journalArticle

Velluto, Diana ; Demurtas, Davide ; Hubbell, Jeffrey A. / PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release : Cyclosporin A as an example. In: Molecular Pharmaceutics. 2008 ; Vol. 5, No. 4. pp. 632-642.
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