Poly(ethylene carbonate)s, part II: degradation mechanisms and parenteral delivery of bioactive agents.
The degradation and drug carrier properties of poly(ethylene carbonate) (PEC) 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 O2-*, which are, in vivo, mostly produced by inflammatory cells. No degradation of PEC was observed in the presence of hydrolases, serum or blood. PEC is biodegraded by surface erosion without significant change in the molecular weight of the residual polymer mass. The non-hydrolytic biodegradation by cells producing O2-* is unique among the polymers used as biodegradable drug carriers. The main degradation product of PEC in aqueous systems is ethylene glycol, formed presumably by hydrolysis of ethylene carbonate. The splitting off of a five-membered ring structure from the polymer chain indicates 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 indicated by a 1:1 correlation between drug release and polymer mass loss.
Stoll
G H
GH
Novartis Pharma AG, CH-4002, Basel, Switzerland.
Nimmerfall
F
F
Acemoglu
M
M
Bodmer
D
D
Bantle
S
S
Müller
I
I
Mahl
A
A
Kolopp
M
M
Tullberg
K
K
D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004343:Drug Implants; D005455:Fluorescent Antibody Technique; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D008970:Molecular Weight; D019999:Pharmaceutical Solutions; D011095:Polyethylenes / Q000737:chemistry*; D011208:Powders; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets
D004337:Drug Carriers; D004343:Drug Implants; D007377:Interleukin-3; D019999:Pharmaceutical Solutions; D011095:Polyethylenes; D011208:Powders; D011994:Recombinant Proteins; D013607:Tablets; C039212:polyethylene carbonate