The present study aimed to investigate the targeting effect of H7K（R2）2-modified pH -sensitive liposomes on U87-MG cells. Using coumarin-6 as a fluorescence probe, we prepared H7K（R2）2-modified p H-sensitive lipos...
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The present study aimed to investigate the targeting effect of H7K（R2）2-modified pH -sensitive liposomes on U87-MG cells. Using coumarin-6 as a fluorescence probe, we prepared H7K（R2）2-modified p H-sensitive liposomes（designated as coumarin-6-PSL-H7K（R2）2）. The flow cytometry assay was used to evaluate the effect of H7K（R2）2 proportions on the cellular uptake and endocytosis pathways of coumarin--6--PSL--H7K（R2）2 on U87-MG cells. The circular dichroism（CD） spectroscopy assay was used to investigate the secondary structures of H7K（R2）2 peptide at pH 7.4 and H 6.8, respectively. Our results indicated that the 2.5% proportion of H7K（R2）2 in the coumarin-6--PSL-H7K（R2）2 was superior to those of 1% and 3.5% of H7K（R2）2. The uptake of coumarin--6-PSL--H7K（R2）2 on U87--MG cells was not inhibited by filipin, M-β--CD or chlorpromazine. The secondary structure of H7K（R2）2 at pH 6.8 was mostly presented as β--turn. In conclusion, we suggested that the appropriate proportion of H7K（R2）2 in the H7K（R2）2--modified pH--sensitive liposomes could be set at 2.5%. The cellular uptake pathway for H7K（R2）2-modified pH--sensitive liposomes was via the cell penetrating capacity of H7K（R2）2 which responded to acidic condition. The secondary structure of H7K（R2）2 at pH 6.8, which was presented as the shape of hairpin, might be mainly responsible for its targeting and cell penetrating effect.
A liquid chromatography with tandem mass spectrometry（LC-MS/MS） method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were ...
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A liquid chromatography with tandem mass spectrometry（LC-MS/MS） method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were analyzed on a Zorbax Extend-C18 column（150 mm×4.6 mm, 5μm）. The mobile phase consisted of a mixture of acetonitrile and deionized water（containing 0.05% formic acid） at a ratio of 27：73（v/v）, and the flow rate was set at 0.8 mL /min. The column temperature was maintained at 30 oC. The LC eluate was detected by an electrospray ionization（ESI） source operated in the positive ion mode, and quantification was conducted using MRM of the transitions m/z 399.24→283.01 and m/z 415.19→178.00 for sunitinib and internal standard（IS, diltiazem hydrochloride）, respectively. The calibration curve was linear in the range of 2–600 ng/m L. The lower limit of quantification was 2 ng/mL. The method also exhibited satisfactory results in terms of sensitivity, specificity, accuracy（with relative error ranging from –4.0% to 1.1%）, precision（with intra- and inter-day relative standard deviations ranging from 2.8% to 9.5%）, matrix effect, recovery as well as stability. Taken together, our newly developed method was reliable to monitor sunitinib concentrations in rabbit plasma.
Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-p...
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Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.
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