An encapsulated drug delivery system for recalcitrant urinary tract infection

J R Soc Interface. 2013 Sep 25;10(89):20130747. doi: 10.1098/rsif.2013.0747. Print 2013 Dec 6.

Abstract

One of the hallmarks of urinary tract infection, a serious global disease, is its tendency to recur. Uropathogenic bacteria can invade cells lining the bladder, where they form longer-term intracellular reservoirs shielded from antibiotics, re-emerging at a later date to initiate flare-ups. In these cases, only lengthy systemic antibiotic treatment can eradicate all the reservoirs. Yet, long courses of antibiotics are not ideal, as they can lead to side effects and an increase in antibiotic resistance. Moreover, most antibiotics lose some potency by the time they reach the bladder, and many cannot permeate cells, so they cannot access intracellular reservoirs. Here, using coaxial electrohydrodynamic forming, we developed novel core-shell capsules containing antibiotics as a prototype for a future product that could be infused directly into the bladder. Gentamicin was encapsulated in a polymeric carrier (polymethylsilsesquioxane) and these capsules killed Enterococcus faecalis, a common chronic uropathogen, in vitro in a dose-responsive, slow-release manner. Capsules containing a fluorescent tracer dye in place of gentamicin penetrated human bladder cells and released their dye cargo with no apparent toxicity, confirming their ability to successfully permeate cells. These results suggest that such antibiotic capsules could prove useful in the treatment of recalcitrant UTI.

Keywords: drug delivery; microbiology; urinary tract infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use
  • Capsules / administration & dosage
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Gentamicins / administration & dosage*
  • Gentamicins / pharmacokinetics
  • Gentamicins / therapeutic use
  • Humans
  • Hydrodynamics
  • Urinary Bladder / metabolism
  • Urinary Tract Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Capsules
  • Delayed-Action Preparations
  • Gentamicins