In vitro and in vivo evaluation of gelatin-chondroitin sulphate hydrogels for controlled release of antibacterial proteins.
Chemically cross-linked gelatin-chondroitin sulphate (ChS) hydrogels, impregnated in Dacron, were evaluated as drug delivery systems for antibacterial proteins. The gelatin-chondroitin sulphate gels, plain or impregnated in Dacron, were cross-linked with a water-soluble carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The release of lysozyme and recombinant thrombocidin (rTC-1), an antibacterial protein derived from human blood platelets, from the gelatin-ChS gels in Dacron in phosphate-buffered saline at 37 degrees C was determined, and compared to the release from gelatin gels in Dacron and plain gelatin-ChS gels. The incorporation of chondroitin sulphate into gelatin gels, caused a marked increase in lysozyme loading capacity, and a slower release rate. The relative release profiles for rTC-1 and lysozyme were equal for cross-linked gelatin as well as for cross-linked gelatin-ChS gels. Furthermore, rTC-1 showed no loss of antibacterial activity after 1 week of release. The lysozyme concentration profiles in the samples and in the surrounding medium as a function of time were calculated using mathematical solutions for Ficks second law of diffusion for a semi-infinite composite medium, which is a schematic representation of a slab in a surrounding medium. The biocompatibility and degradation of the Dacron matrices impregnated with gelatin-ChS gels was studied after implantation in subcutaneous pockets in rats. Chemically cross-linked gelatin-Ch5 gels showed a mild tissue reaction, and almost complete degradation within 18 weeks of implantation.
Kuijpers
A J
AJ
Department of Chemical Technology, Institute of Biomedical Technology, University of Twente, Enschede, Netherlands.
van Wachem
P B
PB
van Luyn
M J
MJ
Brouwer
L A
LA
Engbers
G H
GH
Krijgsveld
J
J
Zaat
S A
SA
Dankert
J
J
Feijen
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D002809:Chondroitin Sulfates / Q000008:administration & dosage*; D005780:Gelatin / Q000008:administration & dosage*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D009113:Muramidase / Q000008:administration & dosage; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D020100:Hydrogels; D011506:Proteins; D005780:Gelatin; D002809:Chondroitin Sulfates; D009113:Muramidase