posted on 2024-01-29, 09:03authored byFlávia
S. C. Rodrigues, Dialina Brilhante, Ana Macêdo, Rita F. Pires, Mónica Faria
Chronic
kidney disease (CKD), a pressing global health issue, affects
millions and leads to end-stage renal disease (ESRD). Hemodialysis
(HD) is a crucial treatment for ESRD, yet its limited efficiency in
removing protein-bound uremic toxins (PBUTs) results in high morbidity
and mortality rates. A high affinity of pharmaceutical drugs for human
serum albumin (HSA) can be leveraged to compete effectively with PBUTs
for the same HSA binding sites, thereby enabling them to be capable
of displacing these toxins. One such drug is ibuprofen (IBF), known
for its very high affinity for HSA and sharing the same binding site
as indoxyl sulfate (IS). This study explores the development of IBF-immobilized
cellulose acetate-based (CA-based) thin films. The films were created
by reacting CA with IBF-modified silica precursors at varying concentrations.
The presence of IBF in CA/TEOS/APTES-IBF-3 and CA/TEOS-IBF-25 films,
containing 3 and 25 wt % IBF, respectively, was confirmed through 1H NMR spectra. Competitive displacement binding assays indicated
that while the incorporation of 3 wt % IBF showed no significant enhancement
in IS displacement, the 25 wt % IBF film increased the dialyzed IS
by 1.3 when normalized to non-IBF films. Furthermore, there was a
1.2-fold decrease in the total percentage of IS, and the free percentage
of IS increased 1.3 to 3.0 times. Although direct systemic infusion
of IBF in HD patients achieves a 2.4 times higher removal of IS, it
is impractical due to the risks it poses to ESRD patients. The IBF-immobilized
films offer the advantage of localized binding, thus eliminating the
need for systemic exposure. This innovative approach lays a foundation
for developing more efficient HD membranes, aiming to address the
challenging issue of PBUT elimination and potentially enhance the
quality of life and treatment outcomes for ESRD patients.