A New Biodegradable Poly-Amino Acid: α,β-Poly[(N-Hydroxypropyl/Aminoethyl)-DL-Aspartamide-co-L-Lysine], A Potential Nonviral Vector for Gene Delivery

Abstract

A new class of biodegradable poly-amino acid, α,β-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°C) solution. PHAAL had lower cytotoxicity than polyethylenimine (25 KDa) and poly-L-Lysine (30 KDa) in Hela, E.C.V-304, Bcap37 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.