Insoluble collagen matrices for prolonged delivery of proteins.
The purpose of this investigation was to evaluate the application of high molecular weight, insoluble collagen as a carrier material for proteins. Matrices were formulated and their behavior in buffer solution was investigated with focus on swelling and inner structure. Cross-linking with glutaraldehyde was introduced prior to the formation of the devices and its influence characterized. In addition, the enzymatic degradation process was studied and release experiments with systems loaded with fluorescent-labeled bovine serum albumin were carried out. Insoluble collagen matrices were characterized by intensive swelling in buffer resulting in development of a coarse porous character. Cross-linking strongly reduced the water penetration, leading to denser structures of the swollen devices. The continuous enzymatic degradation of the disk-shaped matrices by collagenase followed the kinetics of an heterogeneous enzymatic process with hindrance of proteolysis by the addition of glutaraldehyde. Release studies demonstrated that large amounts of model protein were held in the matrices with increased cross-linking degree. In presence of collagenase a prolonged release of the trapped protein over several days by matrix cleavage could be achieved. Insoluble collagen can be effective as a carrier material for proteins with an in vitro release characteristic by both diffusion-controlled and enzymatic degradation mechanisms. Cross-linking at the stage of preparing the aqueous dispersion offers an alternative to subsequent cross-linking processes.
Friess
W
W
Department of Pharmaceutical Technology, University of Erlangen, Germany. wfriess@genetics.com
Lee
G
G
Groves
M J
MJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002021:Buffers; D002417:Cattle; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005612:Freeze Drying; D006868:Hydrolysis; D007213:Indomethacin / Q000008:administration & dosage; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011506:Proteins / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D011506:Proteins; D003094:Collagen; D007213:Indomethacin