Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.
In this review, current understanding of the prevention and treatment of Incontinence Associated Dermatitis (IAD) is discussed. The need for preventative measures which target specific faecal/urinary irritants is highlighted, including the role of urease inhibitors. There is no existing internationally and clinically accepted method to diagnose and categorise the severity of IAD. Diagnosis currently relies on visual inspection; non-invasive techniques to assess skin barrier function could remove subjectiveness, particularly in darker skin tones. Impedance spectroscopy is a non-invasive technique which can be used to monitor skin barrier function, supporting visual assessments. Six studies (2003–2021) which used impedance to assess dermatitis were reviewed; inflamed skin was distinguishable from healthy skin in each case. This suggests that impedance spectroscopy could be useful in diagnosis early-stage IAD, potentially enabling earlier intervention. Finally, the authors present their initial findings on the role of urease in skin breakdown in an in vivo IAD model, using impedance spectroscopy.
We present the concept of a versatile drug-loaded composite
hydrogel
that can be activated using an argon-based cold atmospheric plasma
(CAP) jet to deliver both a drug and CAP-generated molecules, concomitantly,
in a tissue target. To demonstrate this concept, we utilized the antibiotic
gentamicin that is encapsulated in sodium polyacrylate (PAA) particles,
which are dispersed within a poly(vinyl alcohol) (PVA) hydrogel matrix.
The final product is a gentamicin-PAA-PVA composite hydrogel suitable
for an on-demand triggered release using CAP. We show that by activating
using CAP, we can effectively release gentamicin from the hydrogel
and also eradicate the bacteria effectively, both in the planktonic
state and within a biofilm. Besides gentamicin, we also successfully
demonstrate the applicability of the CAP-activated composite hydrogel
loaded with other antimicrobial agents such as cetrimide and silver.
This concept of a composite hydrogel is potentially adaptable to a
range of therapeutics (such as antimicrobials, anticancer agents,
and nanoparticles) and activatable using any dielectric barrier discharge
CAP device.
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