Novel gelatin/alginate soft tissue adhesives loaded with drugs for pain management: structure and properties

Abstract

Interest in tissue adhesives as alternatives for conventional wound closing applications, such as sutures and staples, has increased in the last few decades due to numerous possible advantages, including less discomfort and lower cost. Novel tissue adhesives based on gelatin, with alginate as a polymeric additive and crosslinked by carbodiimide were developed and loaded with two types of drugs for pain relief, bupivacaine and ibuprofen, in order to improve the therapeutic effect. The release of the drugs from the adhesive matrix was found to be controlled mainly by the adhesive’s characteristics, i.e. swelling and hydrophilic group concentration. The drug characteristics, i.e. hydrophilicity and electrical interactions between the drug and the polymeric components, were also found to have some effect. Incorporation of bupivacaine was found to improve the bonding strength of the adhesive due to its inert nature and the reinforcing effect of its fibrous crystals, whereas incorporation of ibuprofen was found to have an adverse effect on the bonding strength, probably due to its reaction with the other adhesive components which increased the crosslinking density. Overall, the novel drug-eluting gelatin-based bioadhesives investigated in this research, especially those loaded with bupivacaine, demonstrated a promising potential for use in wound closing applications.

Keywords:

• gelatin
• alginate
• carbodiimide
• bupivacaine
• ibuprofen
• adhesive
• controlled drug delivery
• bonding strength
• cytotoxicity

Acknowledgments

The authors are grateful to the Office of the Chief Scientist [OCS] in the Israel Ministry of Industry, Trade and Labor for supporting this research and to Ms Ruth Gottlieb, the Department of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Israel for her help in the preparation of cell cultures.