Taste-masked tilmicosin-loaded nanostructured lipid carriers at pilot scale for improved bioavailability and enhanced efficacy against Salmonella infection in swine.

Salmonellosis remains one of the most prevalent bacterial enteric diseases in swine production worldwide. Tilmicosin (TMS) is widely used in swine bacterial infections, but its oral application is limited by gastric degradation and intense bitterness, reducing bioavailability and therapeutic efficacy. This study aimed to develop and evaluate pilot-scale TMS-loaded nanostructured lipid carriers (TMS@NLCs) to overcome these obstacles. Herein, TMS@NLCs were fabricated at 100-L scale via high-pressure homogenization. Physicochemical properties of TMS@NLCs were characterized, along with stability in simulated gastrointestinal fluids and in vitro antibacterial activity. Palatability was assessed by piglet drinking behavior and electronic tongue. Pharmacokinetics and therapeutic efficacy against Salmonella infection were evaluated in piglets. TMS@NLCs exhibited uniform spherical morphology with mean diameter 231.9 ± 33.3 nm, high encapsulation efficiency (95.50 ± 3.31%) and drug loading (4.703 ± 0.179%). Notably, they also showed excellent gastric stability, and superior taste-masking evidenced by reduced bitterness and 34% higher water intake versus commercial TMS solution. TMS@NLCs enhanced intracellular Salmonella clearance and increased oral bioavailability. In Salmonella-infected piglets, TMS@NLCs significantly reduced bacterial loads, attenuated inflammation and restored intestinal barrier, with no detectable adverse effects. Together, pilot-scale TMS@NLCs successfully overcome the inherent limitations of pronounced bitterness and gastric instability associated with the raw drug. This formulation demonstrates exceptional performance in enhancing oral bioavailability and antibacterial efficacy, highlighting its substantial potential for clinical veterinary translation.