Guar gum modified tilmicosin-loaded sodium alginate/gelatin composite nanogels for effective therapy of porcine proliferative enteritis caused by Lawsonia intracellularis

In order to overcome the treatment difficulty of Lawsonia intracellularis (L.intracellularis) using antibiotics, the tilmicosin (TIL)-loaded sodium alginate (SA)/gelatin composite nanogels modified with bioadhesive substances were designed. The optimized nanogels were prepared by electrostatic interaction between SA and gelatin at a mass ratio of 1:1 and CaCl2 as an ionic crosslinker and further modified with guar gum (GG). The optimized TIL-nanogels modified with GG had a uniform spherical shape with a diameter of 18.2 ± 0.3 nm, LC of 29.4 ± 0.2 %, EE of 70.4 ± 1.6 %, PDI of 0.30 ± 0.04, and ZP of −32.2 ± 0.5 mv. The FTIR, DSC, and PXRD showed that GG was covered on the surface of TIL-nanogels in a pattern of staggered arrangements. The TIL-nanogels modified with GG had the strongest adhesive strength amongst those with I-carrageenan and locust bean gum and the plain nanogels, and thus significantly enhanced the cellular uptake and accumulation of TIL via clathrin-mediated endocytosis. It exhibited an increased therapeutic effect against L.intracellularis in vitro and in vivo. This study will provide guidance for developing nanogels for intracellular bacterial infection treatment.