TY - JOUR
T1 - An encapsulated drug delivery system for recalcitrant urinary tract infection
AU - Labbaf, Sheyda
AU - Horsley, Harry
AU - Chang, Ming Wei
AU - Stride, Eleanor
AU - Malone-Lee, James
AU - Edirisinghe, Mohan
AU - Rohn, Jennifer L.
PY - 2013/12/6
Y1 - 2013/12/6
N2 - 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 cargowith 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.
AB - 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 cargowith 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.
KW - Drug delivery
KW - Microbiology
KW - Urinary tract infection
UR - http://www.scopus.com/inward/record.url?scp=84896546180&partnerID=8YFLogxK
U2 - 10.1098/rsif.2013.0747
DO - 10.1098/rsif.2013.0747
M3 - Article
C2 - 24068180
AN - SCOPUS:84896546180
SN - 1742-5689
VL - 10
JO - Journal of The Royal Society Interface
JF - Journal of The Royal Society Interface
IS - 89
ER -