Preparation and evaluation of a linoleic-acid-modified amphiphilic polypeptide copolymer as a carrier for controlled drug release.
In the present study, we describe the synthesis, characterization and self-assembly of a novel amphiphilic linoleic acid (LA)-modified polypeptide copolymer and its drug release behavior in vitro as well. Initially, an amphiphilic ABA triblock copolymer comprising polytetrahydrofuran (PTHF) as a central hydrophobic block and poly(L-lysine)s as outer hydrophilic blocks was prepared via the ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride with a distal amine-terminated PTHF as a macroinitiator, followed by the removal of the protecting group. The resulting triblock copolymer was then reacted with linoleic acid in the presence of N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCHCl)/N-hydroxysuccinimide (HOSu) to give rise to a target LA-modified polypeptide copolymer. It was found to self-assemble into nanoparticles in water. Its critical aggregation concentration was assessed by fluorescence measurement with N-phenyl-1-naphthylamine employed as a molecular probe. The particle sizes of the aggregates were determined by dynamic light scattering, and the aggregate morphologies were evidenced by transmission electron microscopy measurements. Finally, the drug-loading capacity and release behavior in vitro were investigated by using doxorubicin as a model drug.
Tian
Zhen
Z
School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, People's Republic of China.
Zhang
Ai-Ying
AY
Ye
Lin
L
Wang
Meng
M
Feng
Zeng-guo
ZG
D004317:Doxorubicin / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D008027:Light; D019787:Linoleic Acid / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence / Q000379:methods; D013388:Succinimides / Q000737:chemistry; D013696:Temperature
D010455:Peptides; D004364:Pharmaceutical Preparations; D011108:Polymers; D013388:Succinimides; D004317:Doxorubicin; D019787:Linoleic Acid; C001426:N-hydroxysuccinimide