Ischemia−reperfusion (I/R) injury is a disease process that affects several vital organs. There is widespread agreement that the NLRP3 inflammasome pathway plays a crucial role in the development of I/R injury. We have developed transferrinconjugated, pH-responsive nanomicelles for the entrapment of MCC950 drug. These nanomicelles specifically bind to the transferrin receptor 1 (TFR1) expressed on the cells of the blood−brain barrier (BBB) and thus help the cargo to cross the BBB. Furthermore, the therapeutic potential of nanomicelles was assessed using in vitro, in ovo, and in vivo models of I/R injury. Nanomicelles were injected into the common carotid artery (CCA) of a middle cerebral artery occlusion (MCAO) rat model to achieve maximum accretion of nanomicelles into the brain as blood flows toward the brain in the CCA. The current study reveals that the treatment with nanomicelles significantly alleviates the levels of NLRP3 inflammasome biomarkers which were found to be increased in oxygen−glucose deprivation (OGD)-treated SH-SY5Y cells, the I/Rdamaged right vitelline artery (RVA) of chick embryos, and the MCAO rat model. The supplementation with nanomicelles significantly enhanced the overall survival of MCAO rats. Overall, nanomicelles exerted therapeutic effects against I/R injury, which might be due to the suppression of the activation of the NLRP3 inflammasome.
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.
Nanotechnology several time proven effective for the treatment of various diseases. Nano medicine is growing field of research in development of novel drug delivery systems. Targeting autophagy with the help...
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