Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant Ka was 1,639 M-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer

Existence and multiple solutions for a second-order difference boundary value problem via critical point theory

AbstractIn this paper, the critical point theory is employed to establish existence and multiple solutions for a second-order difference boundary value problem

Management strategies of Bring Your Own Device

The rapid development of mobile Internet and mobile terminals promote business office system from PC to mobile terminals gradually. Thus Bring Your Own Device (BYOD) has become one of the important development trends of enterprise office mode. We analyse the driving factors of implementing Bring Your Own Device, then point out some problems in the process of implementing Bring Your Own Device. Further, we propose the corresponding management strategies of Bring Your Own Device in order to provide references for enterprises to meet the need of mobile office

Management strategies of Bring Your Own Device

The rapid development of mobile Internet and mobile terminals promote business office system from PC to mobile terminals gradually. Thus Bring Your Own Device (BYOD) has become one of the important development trends of enterprise office mode. We analyse the driving factors of implementing Bring Your Own Device, then point out some problems in the process of implementing Bring Your Own Device. Further, we propose the corresponding management strategies of Bring Your Own Device in order to provide references for enterprises to meet the need of mobile office

Controllable deposition distance of aligned pattern via dual-nozzle near-field electrospinning

For large area micro/nano pattern printing, multi-nozzle electrohydrodynamic (EHD) printing setup is an efficient method to boost productivity in near-field electrospinning (NFES) process. And controlling EHD multi-jet accurate deposition under the interaction of nozzles and other parameters are crucial concerns during the process. The influence and sensitivity of various parameters such as the needle length, needle spacing, electrode-to-collector distance, voltage etc. on the direct-write patterning performance was investigated by orthogonal experiments with dual-nozzle NFES setup, and then the deposition distance estimated based on a novel model was compared with measurement results and proven. More controllable deposition distance and much denser of aligned naofiber can be achieved by rotating the dual-nozzle setup. This study can be greatly contributed to estimate the deposition distance and helpful to guide the multi-nozzle NFES process to accurate direct-write pattern in manufacturing process in future

Spatial dynamics of a lattice population model with two age classes and maturation delay

This paper is concerned with the spatial dynamics of a monostable delayed age-structured population model in a 2D lattice strip. When there exists no positive equilibrium, we prove the global attractivity of the zero equilibrium. Otherwise, we give some sufficient conditions to guarantee the global attractivity of the unique positive equilibrium by establishing a series of comparison arguments. Furthermore, when those conditions do not hold, we show that the system is uniformly persistent. Finally, the spreading speed, including the upward convergence, is established for the model without the monotonicity of the growth function. The linear determinacy of the spreading speed and its coincidence with the minimal wave speed are also proved

Research on Multinozzle Near-Field Electrospinning Patterned Deposition

Multinozzle electrospinning systems are designed to increase productivity, while near-field electrospinning (NFES) systems are designed to deposit solid nanofibers in a direct, continuous, and controllable manner. In this paper, several multinozzle NFES setups are tested. The experiment reveals that the deposition distance becomes larger when working distance and needle spacing increase, and the influence of voltage is relatively weaker. The deposition of double nozzle NFES has been studied with Coulomb’s law and theoretical derivation has been verified by the experimental conclusion. The experiment result and theoretical derivation are helpful to get different distance of direct-written fibers by adjusting working distance or needle spacing to change distance of fibers largely and adjusting voltage to change distance slowly. Through these efforts, it is convenient to adjust the distance of straight fibers in multinozzle system

Fabrication of three-dimensional micro-nanofiber structures by a novel solution blow spinning device

The fabrication of three-dimensional scaffolds has attracted more attention in tissue engineering. The purpose of this study is to explore a new method for the fabrication of three-dimensional micro-nanofiber structures by combining solution blow spinning and rotating collector. In this study, we successfully fabricated fibers with a minimum diameter of 200 nm and a three-dimensional structure with a maximum porosity of 89.9%. At the same time, the influence of various parameters such as the solvent volatility, the shape of the collector, the feed rate of the solution and the applied gas pressure were studied. It is found that solvent volatility has large effect on the formation of the three-dimensional shape of the structure. The shape of the collector affects the porosity and fiber distribution of the three-dimensional structure. The fiber diameter and fiber uniformity can be controlled by adjusting the solution feed rate and the applied gas pressure. It is feasible to fabricate high-quality three-dimensional micro-nanofiber structure by this new method, which has great potential in tissue engineering