Effects of block length on the enzymatic degradation and erosion of oxazoline linked poly-epsilon-caprolactone.
The aim of the study was to develop enzyme sensitive polymers for pharmaceutical applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O) polymers were synthesized by using epsilon-caprolactone precursors with different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the effects of PCL block length on enzymatic degradation and erosion (weight loss) of PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22 days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O films occurred during incubation, and the erosion of the PCL-O films increased in parallel with a decrease in the PCL block length. The presence of the lipase inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the PCL-O films. These results indicate that lipase was mainly responsible for the enzymatic erosion of the PCL-O films. In comparison, practically no weight loss of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days incubation). The results demonstrate that the studied epsilon-caprolactone based poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be controlled by the PCL block length.
Pulkkinen
Mika
M
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. Mika.Pulkkinen@uku.fi
Malin
Minna
M
Tarvainen
Tommy
T
Saarimäki
Tiina
T
Seppälä
Jukka
J
Järvinen
Kristiina
K
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008970:Molecular Weight; D000077403:Orlistat; D010194:Pancreatin / Q000737:chemistry* / Q000378:metabolism; D010261:Paraoxon / Q000031:analogs & derivatives / Q000494:pharmacology; D011091:Polyesters / Q000138:chemical synthesis* / Q000378:metabolism; D012995:Solubility; D013499:Surface Properties; D013997:Time Factors
C473020:2,2'-bis(2-oxazoline)-linked poly(epsilon-caprolactone); D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D007783:Lactones; D011091:Polyesters; C121104:ethylparaoxon; D010194:Pancreatin; D000077403:Orlistat; D008049:Lipase; D010261:Paraoxon