Application of microfluidic chip technology in pharmaceutical analysis:A review

The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.

Analysis on fat-soluble components of sinapis semina from different habitats by GC-MS

A simple and rapid gas chromatography/mass spectrometry （GC/MS） analysis method was developed for the determination of fat-soluble parts of sinapis semina. Four major compounds were chosen as marker compounds to evaluate the method. Various extraction techniques were evaluated and the greatest efficiency was observed with sonication extraction using diethyl ether. The method was valuated as follows： acceptable apparatus suitability was obtained by testing the resolutions, tailing factors and theoretical plate number of the marker compounds; the precision and reproducibility, expressed as relative standard deviation （RSD）, fell within the prescribed limits. Eight samples of sinapis semina collected from markets in Xi＇an were monitored by using the method. The fingerprints of those samples were analyzed by hierarchical cluster analysis （HCA） similarity analysis. The result indicated that the combination of fingerprint and HCA could be used to analyze sinapis semina from different habitats.

Effective extraction of fluoroquinolones from water using facile modified plant fibers

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from water.Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were fabricated.Compared with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs.The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2%-4.2% within 10 cycles of adsorptiondesorption.A good extraction efficiency of 71.3%-80.9% was achieved after optimizing the extraction condition.Based on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples.High sensitivity with limit of detections of 0.08-0.25 mg/L and good accuracy with recoveries of 83.8%-111.7% were obtained.Overall,the simple and environment-friendly modified waste PFs have potential applications in the effective extraction and detection of FQs in natural waters.

Biointerface engineering of self-protective bionic nanomissiles for targeted synergistic chemotherapy

Erythrocyte membrane(EM)-camouflaged chemotherapeutic delivery nanovehicles hold promise for solid tumor therapy because of their excellent biostability and biocompatibility. However, it is accompanied with insufficient targeting effect and deficient pharmacokinetic behavior due to the lack of a regulated biointerface to navigate and overcome biological transportation obstacles in solid tumor therapy.Herein, an anti-epidermal growth factor receptor(EGFR) aptamer(EApt) modified and EM-cloaked chemotherapeutic nanomissile delivery system was constructed. The anchored-EApt acting as a specific EGFR suppressor promotes to inhibit the overexpression of EGFR and initiate the cell apoptosis. Importantly, the resulting PLGA-DOX@EM-EApt orchestrated the bioactivity of each component and provided synergistic cell apoptosis and antitumor effects by precisely suppressing EGFR expression levels and delivering DOX. The in vitro and in vivo experimental results confirmed that the immune escape and active targeting behaviors of PLGA-DOX@EM-EApt could significantly promote its drug retention and tumor inhibition abilities. Our findings propose a novel strategy using the biointerface functionalization technique, demonstrating a promising therapeutic platform via a biomimetic drug delivery system for precise solid tumor recognition and synergistic therapy.

Recent advances in screening active components from natural products based on bioaffinity techniques

Natural products have provided numerous lead compounds for drug discovery.However,the traditional analytical methods cannot detect most of these active components,especially at their usual low concentrations,from complex natural products.Herein,we reviewed the recent technological advances(2015-2019)related to the separation and screening bioactive components from natural resources,especially the emerging screening methods based on the bioaffinity techniques,including biological chromatography,affinity electrophoresis,affinity mass spectroscopy,and the latest magnetic and optical methods.These screening methods are uniquely advanced compared to other traditional methods,and they can fish out the active components from complex natural products because of the affinity between target and components,without tedious separation works.Therefore,these new tools can reduce the time and cost of the drug discovery process and accelerate the development of more effective and better-targeted therapeutic agents.

EGFR/cell membrane chromatography-online-high performance liquid chromatography/mass spectrometry method for screening EGFR antagonists from Radix Angelicae Pubescentis

The intracellular kinase domains of the epidermal growth factor receptor(EGFR) in some tumor cells are significant targets for drug discovery.We have developed a new EGFR cell membrane chromatography(EGFR/CMC)-online-high performance liquid chromatography/mass spectrometry(HPLC/MS) method for screening anti-EGFR antagonists from medicinal herbs such as Radix Angelicae Pubescentis.In this study,the HEK293 EGFR cells with high expression of EGFR were used to prepare cell membrane stationary phase(CMSP) in the EGFR/CMC model.The retention fractions on the EGFR/CMC model were directly analyzed by combining a 10 port columns switcher with a HPLC/MS system online.As a result,osthole from Radix Angelicae Pubescentis was found to be the active component acting on EGFR like dasatinib as the control drug.There was a good relationship between their inhibiting effects on EGFR secretion and HEK293 EGFR cell growth in vitro.This new EGFR/CMC-online-HPLC/MS method can be applied for screening anti-EGFR antagonists from TCMs,for instance,Radix Angelicae Pubescentis.It will be a useful method for drug discovery with natural medicinal herbs as a leading compound resource.

Accurate construction of cell membrane biomimetic graphene nanodecoys via purposeful surface engineering to improve screening efficiency of active components of traditional Chinese medicine

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.