Nanogels conjugated with cell-penetrating peptide as drug delivery vehicle for treating urinary tract infections

Among hospital-acquired infections, Pseudomonas aeruginosa-associated urinary tract infections (UTIs) are mainly caused by indwelling urethral catheters (catheter-associated UTIs or CAUTIs) and are difficult to treat, resulting in high rates of morbidity among hospitalized patients. While antibiotics can successfully treat bacteria in the bladder lumen, they are inefficient at crossing stratified urothelium plasma membranes to kill persistent intracellular bacterial communities (IBCs). Herein, we introduce an approach to target UTI IBCs by locally delivering the antibiotic gentamicin via polymeric nanogels conjugated with a cell-penetrating peptide Cys-Gly-Lys-Arg-Lys. This novel approach delivered ~36 % more intracellular gentamicin compared to drug delivered in solution in vitro. In an acute UTI murine model, the nanogel cell-penetrating peptide drug delivery system facilitated the transport of gentamicin into the urothelium and resulted in >90 % clearance of a uropathogenic P. aeruginosa clinical strain in vivo.