Curcumin has many pharmacological activities despite its poor bioavailability and in vivo stability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10. This was also reflected in serum cytokine and chemokine levels. At equivalent concentrations, a single oral dose of PLGA-curcumin was more effective in inhibiting serum IFNγ levels and enhancing IL-10 levels than native curcumin. Even at low concentrations, PLGA-curcumin was superior to native curcumin in inhibiting the sequestration of parasitized-RBCs and CD8+ T cells in the brain. A single oral dose of 5 mg PLGA-curcumin containing 350 μg of curcumin resulted in 3–4 fold higher concentration and prolonged presence of curcumin in the brain than that obtained with 5 mg of native curcumin, indicating better bioavailability of PLGA-curcumin. PLGA-curcumin has potential as an adjunct drug to treat human cerebral malaria.
Highly biocompatible,
excellently photostable, nitrogen- and sulfur-containing
novel zwitterionic carbon dots (CDs) were synthesized by microwave-assisted
pyrolysis. The size of CDs were 2–5 nm, with an average size
of 2.61 ± 0.7 nm. CDs were characterized by UV/vis spectroscopy,
fluorescence spectroscopy, zeta potential, Fourier-transform infrared
spectroscopy, X-ray diffraction, and time-resolved fluorescence spectroscopy.
CDs were known to emit blue fluorescence when excited at 360 nm, that
is, UV region, and emit in the blue region of visible spectrum, that
is, at 443 nm. CDs showed excitation-independent photoluminescence
behavior and were highly fluorescent even at lower concentration under
UV light. These CDs were highly fluorescent in nature, with the quantum
yield being as high as 80%, which is comparable to that of organic
dyes. The CDs were further used to image two different oral cancer
cell lines, namely, FaDu (human pharyngeal carcinoma) and Cal-27 (human
tongue carcinoma). The cell viability assay demonstarted that
CDs were highly biocompatible, which was further confirmed by the
side scattering studies as no change in the granularity was observed
even at the highest concentration of 1600 μg/mL. The generation
of reactive oxygen species (ROS) was also investigated and negligible
generaton of ROS was detected. In addition to that, the uptake
phenomenon, cell cycle analysis, exocytosis, and cellular uptake at
4 °C and in the presence of ATP inhibitor were studied. It was
found that CDs easily cross the plasma membrane without hampering
the cellular integrity.
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