The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects

Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and intestinal mucositis in zebrafish

[[abstract]]Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The adverse effects of PLD noted in clinical practice, especially hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical patients suffered from after the administration of PLD. In conclusion, we established a zebrafish model for PLD-induced HFS. The intestinal mucositis simultaneously noted in the PLD-treated zebrafish validated the similarity of clinical courses after administration of PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]GB

Reconfigurable, Wideband, Low-Profile, Circularly Polarized Antenna and Array Enabled by an Artificial Magnetic Conductor Ground

© 1963-2012 IEEE. A reconfigurable, wideband, and low-profile circular polarization (CP) antenna is presented. Its wideband CP reconfigurability is realized by incorporating RF switches into a cross-bowtie radiator. A compact, wide bandwidth, and polarization-independent artificial magnetic conductor ground plane is developed to minimize the overall profile of the antenna while maintaining its wide bandwidth. The simplicity of this single-element design facilitates the realization of a reconfigurable, wide bandwidth CP array that achieves higher directivity without changing its overall profile. Prototypes of the single element and of a 1 × 4 array of these elements were fabricated and tested. The measured results for both prototypes are in good agreement with their simulated values, validating their design principles. They are low profile with a height ∼ 0.05 λ0. The array exhibits a wide fractional operational bandwidth: 1.65 GHz (21.7%), and a high realized gain: 13 dBic. Since they would enhance their channel capacity and avoid polarization mismatch issues, these reconfigurable CP antenna systems are very suitable for modern wireless systems

A Period-Reconfigurable Leaky-Wave Antenna with Fixed-Frequency and Wide-Angle Beam Scanning

© 1963-2012 IEEE. A novel fixed-frequency beam-scanning leaky-wave antenna (LWA) based on a period-reconfigurable structure is presented. Operating at 5 GHz, the antenna consists of a slotted substrate integrated waveguide and 54 electrically small patches. Each patch element is etched with two dumbbell-shaped slots, and its operating state can be flexibly controlled by the biasing of the p-i-n diode on a parasitic strip. An ideal array model employing isotropic point sources is used for the analysis on the scanning mechanism, based on which a new method for suppressing the higher order space harmonics is developed. Using this method, the monoharmonic radiation range can be dramatically extended, and a wide-angle beam scanning can be achieved by manipulating the period length of the LWA. An FPGA controlling platform is designed for the electronic control of the antenna. The measured results validate that the proposed antenna achieves good performance of wide-angle scanning (125°) with a peak gain of 11.8 dBi at a fixed frequency

Cavity-Backed Proximity-Coupled Reconfigurable Microstrip Antenna with Agile Polarizations and Steerable Beams

© 1963-2012 IEEE. A major challenge for a combined reconfigurable antenna is to realize both polarization switching and beam steering independently in a compact antenna structure. A cavity-backed proximity-coupled reconfigurable microstrip antenna proposed in this communication provides an efficient solution. Beam lead p-i-n diodes DSM8100-000 are employed as switching elements to achieve reconfiguration. Three different linear polarizations (0°, 45°, and 90°) are realized by switching the diodes on a proximity-coupled feed network. For each polarization state, the main beam can be steered to three directions by using a reconfigurable parasitic-element network. The parasitic-element network is printed on the same plane of the radiating patch, thereby making the antenna compact. This antenna has nine different working modes, and for all the working modes, the reflection coefficients are below -10 dB with the measured realized gains ranging from 7.2 to 8.1 dBi

Low-profile and wide-beamwidth dual-polarized distributed microstrip antenna

© 2013 IEEE. A low-profile and wide-beamwidth dual-polarized distributed microstrip antenna is presented in this paper. Four isolated micro patches are proposed as the radiation components and are excited by a compact differential-fed network. The micro patches in two diagonals determine the operating frequency bands of the two polarizations, respectively. By increasing the distances between the micro patches, the beamwidth in E plane can be broadened. Shorting poles between the patches and the ground plane are used to achieve good impedance matching. Compact dual-polarized differential-fed networks are also studied and compared with achieve the best antenna performance. To validate the proposed method, a wide-beamwith dual-polarized distributed microstrip antenna, whose dual polarizations operate at 2 and 2.2 GHz, respectively, is manufactured and measured. The external dimensions of the antenna is 70mm × 10 mm (0.49λ × 0.07λ ). The experimental results agree well with the simulated ones. The 3dB beamwidths in E planes reach 116° and 115°, and the gains are 5.15 and 5.5 dB for two polarizations, respectively. Meanwhile, the cross polarizations are less than -26.2 and -27.8 dB. In addition, the impedance bandwidths of 9.2% and 9.9% for VSWR leq 2 are achieved, and the port isolation is greater than 25.4 dB in the bands

Adventitious shoot regeneration from in vitro stem explants of Phellodendron amurense

An efficient in vitro plant regeneration system from stem explants was established in Phellodendron amurense. Factors influencing shoot regeneration from stems including culture medium type, combinations of plant growth regulators and carbon source in the medium were investigated. Adventitious shoot regeneration was significantly influenced by the type of medium. Murashige and Skoog medium (MS) was the best for promoting shoot regeneration, followed by Gamborg medium (B5) and woody plant medium (WPM). The combination of 6-benzyladenine (BA) and naphthaleneacetic acid (NAA) produced better results for shoot regeneration. The optimum shoot regeneration frequency (74.5%) and number of shoots per explant (12.3) was achieved using MS medium supplemented with 29.7 M BA and 5.8 M NAA. High concentrations of BA and NAA in the medium inhibited shoot formation. Among the three sugars tested, 20 g dm-3 glucose was the optimum for shoot regeneration. Rooting of regenerated shoots was successful on 1/4-strength MS medium with the addition of 15.4 M IBA. Almost 100% plantlets survived acclimatization after transferred to soil.Key words: Phellodendron amurense, callus, shoot regeneration, stem explants

Small-Molecule Synthetic Compound Norcantharidin Reverses Multi-Drug Resistance by Regulating Sonic Hedgehog Signaling in Human Breast Cancer Cells

Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells