ABSTRACT
Severe acute pancreatitis (SAP) is characterized by both local and systemic inflammatory responses. This study was designed to develop a site-specific delivery strategy for SAP therapy using celastrol (CLT). First, murine RAW264.7 cells were used as a model of macrophage cell line, cell membranes were obtained by emptying intracellular contents via hypotonic lysing, mechanical membrane disruption, and differential centrifugation. Poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs) were then prepared by sonication. With the collected membrane materials, macrophage membrane coated PEG-PLGA NPs (RNPs) were then prepared by extrusion through a 400 nm polycarbonate membrane. Biodistribution study in rats with SAP showed RNPs selectively accumulated in the inflamed pancreatic tissues. Compared with CLT loaded NPs, CLT loaded RNPs were proven to effectively attenuate local pancreatic inflammation and systemic inflammation in rats with SAP.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the correlation of glucosylceramide synthase (GCS) gene and multidrug resistance 1 (MDR1) gene in inducing multidrug resistance in human multidrug-resistant K562/A02 cell line, and search for a novel strategy for reversing multidrug resistance of leukemia cells.</p><p><b>METHODS</b>The expression levels of GCS and MDR1 mRNA in K562 and K562/A02 cells were assayed by RT-PCR. siRNAs targeting the GCS and MDR1 gene were transfected into K562/A02 cells with liposome, respectively. The differential expression of GCS and MDR1 mRNAs, as well as their correlation, were detected by RT-PCR and real time quantitative-PCR(QPCR).</p><p><b>RESULTS</b>The expression level of GCS and MDR1 mRNA was dramatically lower in drug-sensitive K562 cells compared with the K562/A02 cells. The GCS mRNA was inhibited by 73%(59%-82%) and MDR1 mRNA expression was down regulated by 67% (38%-82%) in K562/A02 cells after being transfected with GCS siRNA. The expression level of MDR1 mRNA was inhibited by 81%(63%-91%) and GCS mRNA expression had no apparent change in K562/A02 cells treated with MDR1 small interference RNA(siRNA).</p><p><b>CONCLUSION</b>Positive correlation was detected between the expression of GCS and MDR1 mRNA in K562/A02 cells and MDR1 mRNA expression was down regulated after silencing the GCS gene expression.</p>