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 language | English |
|---|---|
| Pages (from-to) | 632-642 |
| Number of pages | 11 |
| Journal | Molecular Pharmaceutics |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 1 2008 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release
T2 - Cyclosporin A as an example
AU - Velluto, Diana
AU - Demurtas, Davide
AU - Hubbell, Jeffrey A.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - 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.
AB - 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.
KW - Block copolymer
KW - Cyclosporin A
KW - Nanoparticle
KW - Poly(propylene sulfide)
KW - Polymer micelle
UR - http://www.scopus.com/inward/record.url?scp=51049095142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51049095142&partnerID=8YFLogxK
U2 - 10.1021/mp7001297
DO - 10.1021/mp7001297
M3 - Article
C2 - 18547055
AN - SCOPUS:51049095142
VL - 5
SP - 632
EP - 642
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 4
ER -