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.

Gelatin-Based Materials in Ocular Tissue Engineering

“…Gelatin solutions 15% (w/v) with microbial transglutaminase have been used in vivo in a vitrectomy model (simulating retinal detachment) [137]. The bio-adhesive was seen to successfully cover a retinal tear model 7 days after administration.…”

Current development of biodegradable polymeric materials for biomedical applications

“… 47 Overall, the study shows that this loading bupivacaine in a gelatin/ alginate bioadhesive can potentially be used for wound-closing applications. 47 …”

“… 46 Cohen et al studied novel tissue adhesives based on gelatin, with alginate as a polymeric additive, loaded with bupivacaine or ibuprofen for pain management. 47 They found that the release of drugs from the adhesive matrix was primarily controlled by the gelatin/alginate bioadhesive’s characteristics, such as swelling and hydrophilic group concentrations that can be adjusted by changing the ratio of gelatin to alginate. 47 Moreover, they found that the hydrophilicity and electrical interactions between bupivacaine and ibuprofen with the adhesive components had some effect on the release profile of the drug, and that incorporating bupivacaine improved the bonding strength of the adhesive due to its inert nature whereas ibuprofen decreased the bonding strength due to its reactive nature with the alginate/gelatin adhesive.…”

Recent trends in protein and peptide-based biomaterials for advanced drug delivery

“…Gelatin -based tissue bioadhesives, fabricated alone or with other synthetic and natural polymers, have also been used in drug delivery. Composite tissue adhesives, developed by carbodiimide -mediated crosslinking of gelatin and alginate, were used to entrap the anti-inflammatory drugs bupivacaine and ibuprofen, and the resulting adhesive was used for local pain management [ 310 , 311 ]. Hydrophilicity of the adhesive and its swelling properties control the release of drugs from this matrix.…”