Alginate Microgels Synthesized using Click Chemistry: A Benign Approach for Delivering Beta Lactamase to Gut Microbiota.

Microgels are crosslinked networks of polymer swollen in water with a size of 1-100 µm. Microgels have been extensively studied in the biomedical field due to the ease of engineering structural and mechanical properties. These microgels are typically made from biocompatible polymers such as alginate, agarose, gelatin, etc. which can be easily crosslinked by non-covalent interactions of ionic/hydrogen bonding. However, due to physical crosslinking, these microgels are susceptible to dissolution and degradation. To overcome this issue, generally methacrylate groups are introduced for covalent crosslinking. It requires the generation of free radicals which is unsuitable for biological applications, especially if microgels are used for encapsulating proteins or cells.<br/>Herein, we developed a new system for making mechanically robust microgels using alginate. These microgels are covalently crosslinked using click chemistry, a benign approach. For this, first alkyne/azide functional moieties are introduced on alginate polymer. Then microgels are created with modified alginate using a T-junction microfluidic device. These microgels are robust and remain stable in the buffer for 7 days as opposed to non-covalently crosslinked alginate which dissolves away within hours.<br/>We expect this technology to have many applications, one of which is protein delivery. In this regard, we successfully encapsulated beta-lactamase protein in these alginate microgels without compromising on activity. Beta-lactamase is an interesting protein that can neutralize antibiotics. Antibiotics affect gut microbiome health which increases the risk of secondary infections and antimicrobial resistance. If beta-lactamase is delivered successfully in the gut, it could neutralize the remaining antibiotics post-treatment. Data from the oral delivery of beta-lactamase and other proteins encapsulated in our alginate click microgels will be presented in this talk.