RESUMEN
Most polymeric implants are biodegraded by one of two common chemical degradation mechanisms: (i). hydrolysis and (ii). oxidation. The chemical structure is among the most important factors which affect the biodegradation of polymeric implants. Hydrolytic biodegradations are often accompanied by substantial decrease of pH, whilst oxidative biodegradation processes are usually very slow due to consumption of stoichiometric amounts of oxidising agents. A dramatic acceleration of the biodegradation can be expected, if the biodegradation can be initiated by catalytic amounts of oxidation agents. Poly(ethylene carbonate) (PEC) and poly(trimethylene carbonate) (PTMC) are presumably biodegraded by such catalytic oxidation processes. Their biodegradation shows all the characteristics of surface erosion. Poly(ethylene carbonate) is utilised as a surface eroding biocompatible polymer for controlled delivery of peptide and protein drugs.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Infusiones Parenterales/métodos , Polímeros/química , Polímeros/farmacocinética , Animales , Biotransformación , RatasRESUMEN
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.