TY - JOUR
T1 - Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) copolymer as a carrier for paclitaxel
AU - Lee, Sang Cheon
AU - Kim, Chulhee
AU - Kwon, Ick Chan
AU - Chung, Hesson
AU - Jeong, Seo Young
N1 - Funding Information:
This work was supported by the Korea Institute of Science and Technology through K-2000 program. C.K. thanks Inha Research Fund (22098-01) for support.
PY - 2003/5/20
Y1 - 2003/5/20
N2 - Polymeric micelles based on amphiphilic block copolymers of poly(2-ethyl-2-oxazoline) (PEtOz) and poly(ε-caprolactone) (PCL) were prepared in an aqueous phase. The loading of paclitaxel into PEtOz-PCL micelles was confirmed by 1H-NMR spectra. Paclitaxel was efficiently loaded into PEtOz-PCL micelles using dialysis method, and the loading content of paclitaxel in micelles was in the range 0.5-7.6 wt.% depending on the block composition of block copolymers, organic solvent used in the dialysis, and feed weight ratio of paclitaxel to block copolymer. The higher the content of hydrophobic block in the block copolymers, the higher the loading efficiency of micelles for paclitaxel. When acetonitrile was used as solvent, a higher drug loading efficiency was obtained than with THF. The loading efficiency decreased with increasing feed weight ratio of paclitaxel to block copolymer from 0.1:1 to 0.2:1. The hydrodynamic diameters of paclitaxel-loaded micelles were in the range 18.3-23.4 nm with narrow size distribution. The hemolysis test of PEtOz-PCL performed in vitro indicated that the toxicity of PEtOz-PCLs to lipid membrane was not significant compared with Tween 80, and was comparable to that observed with Cremophore EL. The proliferation inhibition activity of paclitaxel-loaded micelles for KB human epidermoid carcinoma cells was also evaluated in vitro. Paclitaxel-entrapped polymeric micelles exhibited comparable activity to that observed with Cremophore EL-based paclitaxel formulations in inhibiting the growth of KB cells.
AB - Polymeric micelles based on amphiphilic block copolymers of poly(2-ethyl-2-oxazoline) (PEtOz) and poly(ε-caprolactone) (PCL) were prepared in an aqueous phase. The loading of paclitaxel into PEtOz-PCL micelles was confirmed by 1H-NMR spectra. Paclitaxel was efficiently loaded into PEtOz-PCL micelles using dialysis method, and the loading content of paclitaxel in micelles was in the range 0.5-7.6 wt.% depending on the block composition of block copolymers, organic solvent used in the dialysis, and feed weight ratio of paclitaxel to block copolymer. The higher the content of hydrophobic block in the block copolymers, the higher the loading efficiency of micelles for paclitaxel. When acetonitrile was used as solvent, a higher drug loading efficiency was obtained than with THF. The loading efficiency decreased with increasing feed weight ratio of paclitaxel to block copolymer from 0.1:1 to 0.2:1. The hydrodynamic diameters of paclitaxel-loaded micelles were in the range 18.3-23.4 nm with narrow size distribution. The hemolysis test of PEtOz-PCL performed in vitro indicated that the toxicity of PEtOz-PCLs to lipid membrane was not significant compared with Tween 80, and was comparable to that observed with Cremophore EL. The proliferation inhibition activity of paclitaxel-loaded micelles for KB human epidermoid carcinoma cells was also evaluated in vitro. Paclitaxel-entrapped polymeric micelles exhibited comparable activity to that observed with Cremophore EL-based paclitaxel formulations in inhibiting the growth of KB cells.
KW - Amphiphilic block copolymers
KW - Cell growth inhibition
KW - Hemolysis
KW - Paclitaxel
KW - Poly(2-ethyl-2-oxazoline)
KW - Polymeric micelles
UR - http://www.scopus.com/inward/record.url?scp=0038064275&partnerID=8YFLogxK
U2 - 10.1016/S0168-3659(03)00162-7
DO - 10.1016/S0168-3659(03)00162-7
M3 - Article
C2 - 12737846
AN - SCOPUS:0038064275
SN - 0168-3659
VL - 89
SP - 437
EP - 446
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -