Osmotically driven protein release from photo-cross-linked elastomers of poly(trimethylene carbonate) and poly(trimethylene carbonate-co-d,l-lactide).
The potential of osmotic pressure driven release of proteins from poly(trimethylene carbonate) and poly(trimethylene carbonate-co-d,l-lactide) (poly(TMC-co-DLLA)) elastomers with varying amounts of DLLA was investigated using bovine serum albumin (BSA) as a model protein. The BSA was co-lyophilized with either trehalose or trehalose combined with NaCl as osmotigens to produce particles with sufficient osmotic activity. Elastomers composed solely of TMC were not suitable for osmotically driven release when trehalose was the main osmotigen in the solid particles. Copolymerizing TMC with small amounts of DLLA decreased the tear resistance of the elastomer and consequently increased the rate and the total amount of BSA released. Elongation at break played a significant role in determining the osmotic release behavior; elastomers with comparable Young's modulus and tensile strength, but smaller elongation at break, provided faster release rates. Elastomer degradation played a minor role in the osmotic release, as the mechanical properties underwent very little change during the investigated period of release. The poly(TMC-co-DLLA)(80:20) elastomer was able to provide near zero order release of BSA for up to 12days, and the total amount of BSA released was 74+/-4% after 34days, when small amounts of NaCl was added to trehalose. No significant reduction in the microenvironmental pH occurred after 17days of release. TMC elastomers copolymerized with small amounts of DLLA are potential candidates for the localized delivery of acid-sensitive proteins.
Chapanian
R
R
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada. brian.amsden@chee.queensu.ca
Amsden
B G
BG
D055598:Chemical Phenomena; D003432:Cross-Linking Reagents / Q000737:chemistry; D004146:Dioxanes / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods*; D004548:Elasticity; D020724:Elastomers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D009997:Osmotic Pressure; D011108:Polymers / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D012965:Sodium Chloride / Q000737:chemistry; D013499:Surface Properties; D014199:Trehalose / Q000737:chemistry
D003432:Cross-Linking Reagents; D004146:Dioxanes; D004337:Drug Carriers; D020724:Elastomers; D011108:Polymers; D012710:Serum Albumin, Bovine; C059299:polytrimethylene carbonate; C443643:trimethylene carbonate; D012965:Sodium Chloride; C091880:dilactide; D014199:Trehalose