Poly(ethylene glycol)/poly(epsilon-caprolactone) diblock copolymeric nanoparticles for non-viral gene delivery: the role of charge group and molecular weight in particle formation, cytotoxicity and transfection.
Two types of nanoparticles containing pGL3-Control (plasmid DNA) were prepared using nonionic amphiphlic block copolymers and ionic amphiphilic block copolymers containing a terminal cationic group to investigate the effect of charge on the vehicle properties for systemic gene delivery. Methoxy poly(ethylene glycol) (MPEG)/poly(epsilon-caprolactone) (PCL) diblock copolymers were synthesized by the ring-opening polymerizatrion of epsilon-caprolactone in the presence of a catalyst-free MPEG homopolymer. The hydroxy groups of MPEG/PCL block copolymer were then modified into an amine group to synthesize an amine-terminated MPEG/PCL diblock copolymer (AMPEG/PCL). DNA was incorporated into the polymeric nanoparticles by physical entrapment and electrostatic interaction. All nanoparticle samples exhibited spherical structures and although their sizes increased slightly after DNA-loading, they remained less than 160 nm. The AMPEG/PCL nanoparticles exhibited smaller particle sizes than the MPEG/PCL nanoparticles of the same molecular weight after DNA-loading. The optimum mixing ratio of MPEG/PCL and AMPEG/PCL copolymers to DNA ranged from 4:1 to 1:2 depending on the molecular weight of the block copolymer, the composition of MPEG and PCL and terminal amine group. Based on in vitro cytotoxicity tests, the DNA-loaded MPEG/PCL and AMPEG/PCL nanoparticles did not induce any remarkable cytotoxicity against normal human fibroblasts. Transfection efficiencies of DNA-loaded nanoparticles were improved about 3.4 - 12.9 times under serum conditions.
Jang
Jeong Soon
JS
School of Chemical Engineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
Kim
So Yeon
SY
Lee
Sang Bong
SB
Kim
Kyung Ok
KO
Han
Joong Soo
JS
Lee
Young Moo
YM
D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008297:Male; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D014162:Transfection / Q000379:methods*
D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols