2 research outputs found
Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis
Ulcerative colitis is a multifactorial disease of the
gastrointestinal
tract which is caused due to chronic inflammation in the colon; it
usually starts from the lower end of the colon and may spread to other
portions of the large intestine, if left unmanaged. Budesonide (BUD)
is a synthetically available second-generation corticosteroidal drug
with potent local anti-inflammatory activity. The pharmacokinetic
properties, such as extensive first-pass metabolism and quite limited
bioavailability, reduce its therapeutic efficacy. To overcome the
limitations, nanosized micelles were developed in this study by conjugating
stearic acid with caffeic acid to make an amphiphilic compound. The
aim of the present study was to evaluate the pharmacological potential
of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced
colitis. Micelles were formulated by the solvent evaporation method,
and their physicochemical characterizations show their spherical shape
under microscopic techniques like atomic force microscopy, transmission
electron microscopy, and scanning electron microscopy. The in vitro
release experiment shows sustained release behavior in physiological
media. These micelles show cytocompatible behavior against hTERT-BJ
cells up to 500 μg/mL dose, evidenced by more than 85% viable
cells. BUD-loaded micelles successfully normalized the disease activity
index and physical observation of colon length. The treatment with
BUD-loaded micelles alleviates the colitis severity as analyzed in
histopathology and efficiently, overcoming the disease severity via
downregulation of various related cytokines (MPO, NO, and TNF-α)
and inflammatory enzymes such as COX-2 and iNOS. Results of the study
suggest that BUD-loaded nano-sized micelles effectively attenuate
the disease conditions in colitis
Highly Biocompatible Smart Injectable Hydrogel for the Management of Rheumatoid Arthritis
Rheumatoid
arthritis (RA) is a chronic inflammatory disease
that
severely affects joints and restricts locomotion. Various treatment
regimens are available for RA, providing short-term relief from pain,
but long-term relief from the disease is still not available. Evidently,
cytokines play a crucial role in the pathophysiology of the disease.
However, aberrant immune responses, genetic dispositions, viral infections,
or toxicants are some possible causative mediators of RA. The synovial
fluid of rheumatoid arthritis patients encompass cytokines, especially
osteoclastogenic cytokines, and invasion factors such as macrophage
colony-stimulating factor (M-CSF) and the receptor activator of NF-κB
ligand (RANKL). Moreover, tumor necrosis factor-α (TNF-α)
and interleukins (IL-1, 6, and 17) intensify osteoclast differentiation
and activation. Therefore, in order to restrict the cytokine expression,
we used budesonide as a therapeutic lead and encapsulated it into
a highly biocompatible hydrogel system. The hydrogel system developed
by us is enzyme-responsive and provides sustained drug release flow
over an extended period of time. This hydrogel is characterized by
ζ-potential analysis, field-emission scanning electron microscopy
(FE-SEM), and attenuated total reflectance-Fourier transform infrared
(ATR-FTIR) spectroscopy, and it is further encapsulated with budesonide
(glucocorticoids) for therapeutic purposes. Evidently, Bud-loaded
ER-hydrogel showed improvement in joint physiology compared to the
disease group and downregulated the inflammatory markers