Synthesis and in vitro Property Study of Polyaspartamides

Abstract

Cationic polyaspartamides including poly‐α,β‐[N′‐(2‐aminoethy1)‐L‐aspartamide] (PAEA), poly‐α,β‐[N′‐(4‐aminobutyl)‐L‐aspartamide] (PABA), poly‐α,β‐[N′‐(6‐aminohexyl)‐L‐aspartamide] (PAHA), poly‐α,β‐[N′‐(5‐amino‐3‐azapentyl)‐L‐aspartamide] (PAAPA) and poly‐α,β‐[N′‐(8‐amino‐3,6‐diazaoctyl)‐L‐aspartamide] (PADAOA) were synthesized from polysuccinimide. Their properties were evaluated by 1H NMR, IR, GPC, fluorescence measurement and in vitro cytotoxicity assays. The molecular weights per primary amine charge group of PAEA(1) (Mn=2229), PAAPA and PADAOA are 212, 279, and 226. Polyaspartamides including PAEA(1), PAAPA, PADAOA and low molecular weight PAHA are markedly less toxic than poly(ethyleneimine) and poly(L‐lysine), however, PABA and higher molecular weight PAHA are slightly less toxic than poly(L‐lysine). Cell cytotoxicity of PAHA was seen to decrease with increasing molecular weight of PAHA, due to water solubility reduction. The negatively charged plasmid DNA has been found to be completely neutralized and complexed by the cationic polyaspartamides at an N/P ratio of 5:1 to 10:1, forming self‐assembled polyplexes via ionic interactions. These polyaspartamide/DNA complexes possess stable zeta potentials and mean particle diameters of about 180 nm for PAEA (1)/DNA and PAAPA/DNA complexes and 280 nm for PADAOA/DNA complexes.

Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

“…DTPA mono(hydroxysuccinimidyl ester) (SuO-DTPA), poly-␣,␤-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA) (Yan et al, , 2007c and 5-(4 -aminophenyl)-10,15,20-tris(4 -sulfonatophenyl) porphyrin, trisodium salt (APTSPP) (Yan et al, 2007a) were synthesized according to the cited literature. The injection solution of Gd-DTPA (Magnevist, Gadopentetic acid dimeglumine salt injection) was purchased from the Bayer Schering Pharmacy Division, Bayer HealthCare Company Limited, Germany.…”

“…As reported, antiviral drugs and anti-inflammatory agents were covalently linked to poly-␣,␤-[N-(2-hydroxyethyl)-d,l-aspartamide] (PHEA) forming drug-polymer conjugates capable of increasing drug stability and bioavailility. Therefore polyaspartamide can also be used as the polymer carrier for MRI contrast agents (Giammona et al, 1992(Giammona et al, , 1998Yan et al, , 2007c.…”

Dendrimers as carriers for contrast agents in magnetic resonance imaging

“…Some biological molecules including monoclonal antibodies, albumin, protein, polysaccharide and dextrans, and some synthetic polymers such as poly (amino acid) and dendrimers, have also been investigated as polymer carriers for MRI contrast agents [5][6][7][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36].…”

Polyaspartamide spin probes containing isoindoline nitroxide and porphyrin groups

“…The polyaspartamide isoindoline nitroxides had higher relaxation effectiveness and had greater toxicity to HeLa cells than that of 5-carboxy-1,1,3,3-tetramethylisoindolin-2yloxyl. [16][17][18][19][20][21] Several specific tumor-selective molecules, including monoclonal antibodies, protein, avidin, vitamin, peptide, and porphyrin, have been investigated to increase the site-specific accumulation of MRI contrast agents and anticancer drugs in tumor cells. The electron paramagnetic resonance spectra of polyaspartamide isoindoline nitroxides exhibited characteristic hyperfine electron paramagnetic resonance spectra of tetramethyl isoindoline nitroxides, with typical nitroxide g-values and nitrogen isotropic hyperfine coupling constants.…”

“…Moreover, EPRI can be used to study the tumor hypoxia, tissue heterogenicity with respect to oxygen and redox status, and vascular deficiencies in vivo. [16][17][18][19][20][21] Several specific tumor-selective molecules, including monoclonal antibodies, protein, avidin, vitamin, peptide, and porphyrin, have been investigated to increase the site-specific accumulation of MRI contrast agents and anticancer drugs in tumor cells. It is normally necessary to introduce spin probes into the system by intravenous or intramuscular infusion of stable but slowly metabolizable nontoxic water-soluble paramagnetic materials or stable implantable particulate materials.…”