title: In vivo implantation of 2,2'-bis(oxazoline)-linked poly-epsilon-caprolactone: proof for enzyme sensitive surface erosion and biocompatibility.
abstract: Previously, we have demonstrated that 2,2-bis(2-oxazoline) linked poly-epsilon-caprolactone (PCL-O) is degraded in vitro enzymatically by surface erosion which could enable the novel use of this material for drug delivery and other biomedical applications. In this study, degradation, erosion (weight loss) and toxicity of PCL-O poly(ester-amide)s were evaluated in vivo. PCL and three PCL-O polymers with different PCL block lengths (M(n): 1500, 3900, 7500 g/mol) were melt-pressed in the form of discs and implanted subcutaneously in Wistar rats (dose approximately 340 mg/kg) for 1, 4 and 12 weeks. With implantation for 12 weeks, up to 16.5% weight loss of polymer discs was measured for the most extensively linked PCL-O polymer (block length 1500 g/mol) whereas practically no weight loss was observed with the other polymers. NMR, DSC and SEC studies as well as SEM micrographs before and after implantation and in vitro hydrolysis studies indicate that enzyme based surface erosion of PCL-O polymers occurred in vivo. The in vivo evaluation based on results from hematology, clinical chemistry and histology of the implantation area and main organs (i.e. heart, lung, liver, kidney, spleen and brain) demonstrated that PCL-O polymers are biocompatible and safe, enzyme sensitive biomaterials.
authors.affiliation: Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. Mika.Pulkkinen@uku.fi
authors.forename: Mika
authors.initials: M
authors.lastname: Pulkkinen
authors.forename: Minna
authors.initials: M
authors.lastname: Malin
authors.forename: Jan
authors.initials: J
authors.lastname: Böhm
authors.forename: Tommy
authors.initials: T
authors.lastname: Tarvainen
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Jukka
authors.initials: J
authors.lastname: Seppälä
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000825:Animal Structures / Q000033:anatomy & histology; D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight; D002021:Buffers; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D020007:Implants, Experimental / Q000009:adverse effects; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009929:Organ Size; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D040521:Subcutaneous Tissue / Q000473:pathology; D013499:Surface Properties; D044366:Transition Temperature
chemical_list: C473020:2,2'-bis(2-oxazoline)-linked poly(epsilon-caprolactone); D002021:Buffers; D004798:Enzymes; D011091:Polyesters; C016240:polycaprolactone