Gh. Stoll et al., Poly(ethylene carbonate)s, part II: degradation mechanisms and parenteral delivery of bioactive agents, J CONTR REL, 76(3), 2001, pp. 209-225
The degradation and drug carrier properties of poly(ethylene carbonate) (PE
C) were investigated in vitro and in rats and rabbits. PEC was found to be
specifically degraded in vivo and in vitro by superoxide radical anions O-2
(-)., which are, in vivo, mostly produced by inflammatory cells. No degrada
tion of PEC was observed in the presence of hydrolases, serum or blood. PEC
is biodegraded by surface erosion without significant change in the molecu
lar weight of the residual polymer mass. The non-hydrolytic biodegradation
by cells producing O-2 . is unique among the polymers used as biodegradable
drug carriers. The main degradation product of PEC in aqueous systems is e
thylene glycol, formed presumably by hydrolysis of ethylene carbonate. The
splitting off of a five-membered ring structure from the polymer chain indi
cates a chain reaction mechanism for the biodegradation. PEC is a suitable
drug carrier, particularly for labile drugs. Using human interleukin-3 and
octreotide as model drugs, surface erosion of the PEC formulations was indi
cated by a 1:1 correlation between drug release and polymer mass loss. (C)
2001 Elsevier Science BY. All rights reserved.