In vitro and in vivo evaluation of gelatin–chondroitin sulphate hydrogels for controlled release of antibacterial proteins

• Published in: Biomaterials Vol. 21; no. 17; pp. 1763 - 1772
• Main Authors: Kuijpers, A.J, van Wachem, P.B, van Luyn, M.J.A, Brouwer, L.A, Engbers, G.H.M, Krijgsveld, J, Zaat, S.A.J, Dankert, J, Feijen, J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2000; Elsevier Science
• Subjects: Animals; Anti-Infective Agents - administration & dosage; Biocompatibility; Biocompatible Materials; Biodegradation; Biological and medical sciences; Chondroitin Sulfates - administration & dosage; Chondroitin sulphate; Controlled drug delivery; Cross-linking; Crosslinking; Drug delivery; Enzymes; Gelatin; Gelatin - administration & dosage; Humans; Hydrogels; Hydrogels - administration & dosage; In Vitro Techniques; Male; Medical sciences; Muramidase - administration & dosage; Nitrogen compounds; Proteins - administration & dosage; Rats; Rats, Wistar; Sulfur compounds; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Tissue reaction; Biodegradation; Drug delivery; Tissue reaction; Chondroitin sulphate; Gelatin; Cross-linking; Rat; Biodegradability; Controlled release form; Chemical method; Rodentia; Crosslinking; In vitro; In vivo; Implanted material; Vertebrata; Mammalia; Animal; Chondroitin sulfate; Hydrogel; Antibacterial agent; Biomedical engineering
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/S0142-9612(00)00064-8

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°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–ChS gels showed a mild tissue reaction, and almost complete degradation within 18 weeks of implantation.