Novel drug delivery approach shows promise for UTI

A novel approach to treating urinary tract infections (UTIs) showed promise in preclinical models, according to data published in Nanomedicine.¹

The method involves local delivery of the antibiotic gentamicin (Gentak) directly into the bladder tissue.

The method was well-tolerated, with minimal adverse events and a large safe dosage range.

According to the authors, “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).”

Thus, the investigators developed a method to target UTI IBCs using intravesically-delivered (I-VESIC) polymeric nanogels that are conjugated with a cell-penetrating peptide (CPP) Cys-Gly-Lys-Arg-Lys. The nanogel includes 2-hydroxyethyl acrylate, tetraethyl dimethacrylate, and acrylic acid (HTA) monomers synthesized “in 4× solvent ratio at ~70 % double-bond conversion,” according to the authors.

"We believe this new approach offers a more effective treatment by delivering the drug directly to the infected cells, allowing it to precisely target and eliminate the infection,” explained co-author Devatha Nair, PhD, an associate professor in craniofacial biology at the University of Colorado School of Dental Medicine, Aurora, in a news release on the findings.² “This method minimizes side effects and reduces the risk of antibiotic resistance. In contrast, current antibiotics may require prolonged or repeated therapy to be effective, which can contribute to resistance and cause harmful side effects, especially in organs like the kidneys.”

Overall, data from the study showed that this method was able to facilitate a 36% increase in intracellular gentamicin delivered inside urothelial cells compared with delivery via a solution in vitro. In an acute UTI murine model, the approach resulted in a greater than 90% clearance of a uropathogenic P. aeruginosa clinical strain in vivo.

Maximum drug release was also sustained up to 8 hours, with gradual decline from hours 12 to 96.

The investigators also noted that the method was well-tolerated, with minimal adverse events and a large safe dosage range. There was no significant effect on the cell’s metabolism vs untreated cells at up to 1 mg HTA-CPP (P > .05) after 24 hours of exposure. “In contrast, 10 mg HTA-CPP decreased the cellular metabolic activity significantly to ~19% compared to the untreated cells (P < .0001),” the authors wrote.

Based on these findings, the authors say this approach holds promise for the treatment of patients with recurrent UTIs.

“We prove not only that this technology is doable but could be very effective for future clinical use and can potentially lead towards an eventual cure of recurrent infections,” concluded senior author Michael Schurr, PhD, an associate professor in the department of immunology & microbiology at the University of Colorado School of Medicine, in the news release.² “This is an exciting advancement for the delivery of medicine and the potential to improve the quality of life for many people. For urinary tract infections, they are not only common and costly but also debilitating, severely affecting the quality of life for those who suffer from them. Advancing research to develop more effective, long-lasting treatments is a crucial step in enhancing overall health and well-being.”

REFERENCES

1. Escobedo H, Zawadzki N, Till JKA, et al. Nanogels conjugated with cell-penetrating peptide as drug delivery vehicle for treating urinary tract infections. Nanomedicine. 2025:65:102812. doi:10.1016/j.nano.2025.102812

2. Promising new research shows potential to cure recurrent urinary tract infections. News release. University of Colorado Anschutz Medical Campus. Published online and accessed March 12, 2025. https://www.eurekalert.org/news-releases/1076708