Degradation of and drug release from a novel 2,2-bis(2-oxazoline) linked poly(lactic acid) polymer.
The degradation rate of poly(lactic acid) (PLA) is typically modified by copolymerization of the glycolide with lactide. In the present study, the degradation rate of PDLLA was modified by a novel linking of PLA with 2,2'-bis(2-oxazoline). This modification resulted in formation of a more rapidly degrading poly(ester amide) (PEA) for controlled drug release. The hydrolytic degradation of PDLLA and PEA films was studied in PBS (pH 7.4, USP XXIV, 37 degrees C); the resulting decrease in molecular weight was determined by size exclusion chromatography and the weight loss of films was measured. Drug releases of guaifenesin (mw 198.2), timolol (mw 332.4), sodium salicylate (mw 160.1) and FITC-dextran (mw 4400) from PDLLA and PEA films and microspheres were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PEA was substantially greater than that of PDLLA. The release profiles of all small model drugs (mw <332.4) from PDLLA films were biphasic or triphasic, while the release profiles of small model drugs from PEA films varied extensively. Due to the faster weight loss of PEA, FITC-dextran (mw 4400) was released substantially more rapidly from PEA microspheres than from PDLLA microspheres. In conclusion, all model drugs, except guaifenesin, were released faster from PEA preparations than from PDLLA preparations.
Tarvainen
Tommy
T
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, Kuopio, Finland. tommy.tarvainen@uku.fi
Karjalainen
Teija
T
Malin
Minna
M
Pohjolainen
Satu
S
Tuominen
Jukka
J
Seppälä
Jukka
J
Järvinen
Kristiina
K
D001672:Biocompatible Materials / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006140:Guaifenesin / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D008970:Molecular Weight; D010080:Oxazoles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012980:Sodium Salicylate / Q000737:chemistry; D013997:Time Factors; D013999:Timolol / Q000737:chemistry
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D010080:Oxazoles; D011091:Polyesters; D011108:Polymers; C015219:fluorescein isothiocyanate dextran; D019344:Lactic Acid; C033616:poly(lactide); D006140:Guaifenesin; D013999:Timolol; D016650:Fluorescein-5-isothiocyanate; D012980:Sodium Salicylate