An encapsulated drug delivery system for recalcitrant urinary tract infection

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.

Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection

“…The protocol for the extended antibacterial assay was similar to that previously reported [32]. Briefly, an overnight culture of E. faecalis clinical strain EF36 (isolated directly from a patient with chronic UTI [12], in TSB was adjusted to the equivalent of a 0.5 McFarland standard using CnT Prime bladder epithelial media (CELLnTEC, Switzerland).…”

Novel targeted bladder drug-delivery systems: a review

“…There are pilot data showing the feasibility of loading an antibiotic into a non-cell-toxic microcapsule that can both penetrate bladder cells and provide slow release of the drug that retains its bactericidal properties. 67 This system has been developed for the delivery of high doses of antibiotic to treat recalcitrant UTIs. The capsules have been prepared with coaxial electrohydrodynamic forming technology, which has shown considerable promise for the production of fibers and particles at the micro- and nanoscale.…”

Electrosprayed microparticles for intestinal delivery of prednisolone

“…Electrospraying has been investigated thoroughly as a potential technique for pharmaceutical applications [ 19 ] and more specifically for dissolution enhancement of water-insoluble drugs by facilitating preparation of the drug delivery system at reduced size [ 20 ], where a higher surface area to volume ratio greatly favours the rate at which the incorporated drug is released [ 21 , 22 ]. In a study by Zhang et al .…”

“…Electrospraying has been investigated thoroughly as a potential technique for pharmaceutical applications [19] and more specifically for dissolution enhancement of water-insoluble drugs by facilitating preparation of the drug delivery system at reduced size [20], where a higher surface area to volume ratio greatly favours the rate at which the incorporated drug is released [21,22]. In a study by Zhang et al [23], it was reported that using coaxial electrospraying for preparation of a griseofulvin formulation using Eudragit L100 as an encapsulating carrier significantly enhanced the dissolution and absorption behaviour of the poorly water-soluble drug.…”