Enhanced Cellular Delivery of Tildipirosin by Xanthan Gum-Gelatin Composite Nanogels.

Tildipirosin has no significant inhibitory effect on intracellular bacteria because of its poor membrane permeability. To this end, tildipirosin-loaded xanthan gum-gelatin composite nanogels were innovatively prepared to improve the cellular uptake efficiency. The formation of the nanogels via interactions between the positively charged gelatin and the negatively charged xanthan gum was confirmed by powder X-ray diffraction and Fourier transform infrared. The results indicate that the optimal tildipirosin composite nanogels possessed a 3D network structure and were shaped like a uniformly dispersed ellipse, and the particle size, PDI, and ζ potential were 229.4 ± 1.5 nm, 0.26 ± 0.04, and -33.2 ± 2.2 mV, respectively. Interestingly, the nanogels exhibited gelatinase-responsive characteristics, robust cellular uptake via clathrin-mediated endocytosis, and excellent sustained release. With those pharmaceutical properties provided by xanthan gum-gelatin composite nanogels, the anti- Staphylococcus aureus activity of tildipirosin was remarkably amplified. Further, tildipirosin composite nanogels demonstrated good biocompatibility and low in vivo and in vitro toxicities. Therefore, we concluded that tildipirosin-loaded xanthan gum-gelatin composite nanogels might be employed as a potentially effective gelatinase-responsive drug delivery for intracellular bacterial infection.