Hyaluronic Acid-Functionalized Alginate Microspheres via Electrospraying for CD44-Mediated Targeted Delivery of...

Probiotic delivery faces challenges in maintaining bacterial viability and achieving precise targeting of the gastrointestinal tract. In this study, alginate microspheres (ALG MSs) encapsulating Clostridium butyricum (CB) were fabricated using electrospray technology. Hyaluronic acid (HA) was used to modify both the microspheres and the CB surface to enable targeted delivery through the receptor-ligand interaction between HA and CD44. The resulting CB^HA@ALG^HA MSs exhibited an encapsulation efficiency of 69.23 ± 7.30% and a postdigestion survival rate of 94.56 ± 4.87%. HA modification enhanced adhesion to inflamed Caco-2 cells by 2.7- and 2.3-fold for microspheres and CB, respectively. In vivo fluorescence imaging confirmed a 1.7-fold increase in targeted accumulation at CD44-overexpressing inflamed colonic sites. Oral administration of CB^HA@ALG^HA MSs alleviated DSS-induced colitis, elevated short-chain fatty acids, restored barrier integrity, and improved gut microbial balance. This strategy ensures probiotic viability and enables inflammation-targeted colonic delivery for advanced probiotic applications.