A new biodegradable poly-amino acid: alpha,beta-poly[(N-hydroxypropyl/aminoethyl)-DL-aspartamide-co-L-lysine], a potential nonviral vector for gene delivery.
A new class of biodegradable poly-amino acid, alpha,beta-poly[(N-hydroxypropyl/aminoethyl)-DL-Aspartamide-co-L-Lysine] (PHAAL), was synthesized by ring-opening of poly[succinimide-co-lysine](PSL) with n-propanolamine and ethylene diamine after thermal copolycondensation of DL-Aspartic acid and L-lysine under reduced pressure. Different ratio feeds of PSL were obtained and characterized by 1H-NMR, Fourier transformed infrared spectroscopy, X-ray, thermogravimetric analysis and gel permeation chromatography experiments. As one of the polycationic materials, performed for gene delivery carrier, the PHAAL degradation experiment was carried out in PBS (10 mM, pH =7.4) and enzyme (papain, trypsine 1 mg/ml, 37 +/- 0.1 degree C) solution. PHAAL had lower cytotoxicity than polyethylenimine (25KDa) and poly-L-Lysine (30 KDa), in Hela, E.C.V.-304, Bcap 37 cell lines. Particle size and zeta, potential of PHAAL/DNA complexes were measured. Sizes ranged from 300-500 nm and zeta potentials were at -20 to 2,5 mV. The condensation ability of PHAAL for DNA was evaluated by agarose gel electrophoresis. The PHAAL could completely neutralize DNA at N/P ratio (w/w) 150:1.
Guping
Yangzhi
Y
College of Pharmaceutical Science, Zhejiang University, 117602 Singapore.
Guping
Tang
T
Yànjie
D001224:Aspartic Acid / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D001704:Biopolymers; D001711:Biotransformation; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D011107:Polylysine / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D011506:Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics
D001704:Biopolymers; D010455:Peptides; D011506:Proteins; C499773:alpha,beta-poly(aspartic acid); D011107:Polylysine; C017645:polyaspartate; D001224:Aspartic Acid