To
develop a drug delivery system (DDS), it is critical to address
challenging tasks such as the delivery of hydrophobic and amphiphilic
compounds, cell uptake, and the metabolic fate of the drug delivery
carrier. Low-density lipoprotein (LDL) has been acknowledged as the
human serum transporter of natively abundant lipoparticles such as
cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo
B) is the only protein contained in LDL, and possesses a binding moiety
for the LDL receptor that can be internalized and degraded naturally
by the cell. Therefore, synthetic/reconstituting apoB lipoparticle
(rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic
materials. Here, we synthesized rABL in vitro, using full-length apoB
through a five-step solvent exchange method, and addressed its potential
as a DDS. Our rABL exhibited good biocompatibility when evaluated
with cytotoxicity and cell metabolic response assays, and was stable
during storage in phosphate-buffered saline at 4 °C for several
months. Furthermore, hydrophobic superparamagnetic iron oxide nanoparticles
(SPIONPs) and the anticancer drug M4N (tetra-O-methyl nordihydroguaiaretic
acid), used as an imaging enhancer and lipophilic drug model, respectively,
were incorporated into the rABL, leading to the formation of SPIONPs-
and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier
transform infrared spectroscopy suggested that rABL has a similar
composition to that of LDL, and successfully incorporated SPIONPs
or M4N. SPIO@rABL presented significant hepatic contrast enhancement
in T2-weighted magnetic resonance imaging
in BALB/c mice, suggesting its potential application as a medical
imaging contrast agent. M4N@rABL could reduce the viability of the
cancer cell line A549. Interestingly, we developed solution-phase
high-resolution transmission electron microscopy to observe both LDL
and SPIO@rABL in the liquid state. In summary, our LDL-based DDS,
rABL, has significant potential as a novel DDS for hydrophobic and
amphiphilic materials, with good cell internalization properties and
metabolicity.
Corbicula fluminea, the primary freshwater bivalve cultivated in Taiwan, was formerly used as a remedy for hepatitis. Recent reports indicate that C. fluminea has many bioactivities, but it remains unknown whether C. fluminea affects inflammation. This study explored the anti-inflammatory activity of C. fluminea. C. fluminea was first treated with chloroform to obtain clam chloroform extracts (CCEs). On the basis of the assay for the release of pro-inflammatory cytokines in vitro and in vivo, the results show that the CCEs significantly lowered the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines. Additionally, the CCEs reduced LPS-induced organ damage. Real-time polymerase chain reaction analysis suggested that CCEs inhibit the LPS-induced mRNA expression of interleukin-1β and tumor necrosis factor-α. Western blot analysis indicated that the CCEs increased expression of IκB and attenuated the phosphorylation of IκB. Gas chromatography−mass spectrometry suggests that phytosterols and fatty acids are responsible for the anti-inflammatory properties of CCEs. Taken together, CCEs have the potential to be developed as an anti-inflammatory functional food.
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