P. Ferruti et al., Amphoteric linear poly(amido-amine)s as endosomolytic polymers: Correlation between physicochemical and biological properties, MACROMOLEC, 33(21), 2000, pp. 7793-7800
Five poly(amido amine)s (PAAs) carrying two ter-amino groups and one carbox
yl group per repeating unit were prepared by hydrogen-transfer polyaddition
of a-methylpiperazine (ISA 23), 1,2-bis(N-methylamino)ethane (DMEDA-BAC),
1,2-bis(N-ethylamino)ethane (DEEDA-BAC, 1,3-bis(N-methylamino)propane (DMEP
DA-BAC), or 1,6-bis(N-methylamino)hexane (DMEXA-BAC), in each case to 2,2-b
is(acrylamido)acetic acid (BAC). The resultant PAAs had an M-n in the range
7 985-24 980 g/mole and an M-w in the range 11 420-42 710 g/mole. Consider
able differences were observed in the basicity of the amino groups present
(log K(1)degrees = 7.5-9.5; log K(2)degrees = 3.2-8.4), whereas the log K(3
)degrees value (2-3) of the carboxyl groups was consistent with that of a f
airly strong acid. DEEDA-BAC, DMEDA-BAC, and ISA 23 were nontoxic (IC50 > 5
mg/mL). Those PAAs with the highest log K(2)degrees values were more cytot
oxic (IC50 = 3.55 mg/mL for DMEPDA-BAC, and IC50 = 0.23 m/mL for DMEXA-BAC)
. All the PAAs displayed pH-dependent haemolysis (most lytic at pH 5.5), co
nsistent with their proposed use as endosomolytic polymers.