An Artificial Gut/Absorption Simulator: Understanding the Impact of Absorption on In Vitro Dissolution, Speciation, and Precipitation of Amorphous Solid Dispersions.

Upon dissolution, amorphous solid dispersions (ASDs) of poorly water-soluble compounds can generate supersaturated solutions consisting of bound and free drug species that are in dynamic equilibrium with each other. Only free drug is available for absorption. Drug species bound to bile micelles, polymer excipients, and amorphous and crystalline precipitate can reduce the drug solute's activity to permeate, but they can also serve as reservoirs to replenish free drug in solution lost to absorption. However, with multiple processes of dissolution, absorption, and speciation occurring simultaneously, it may become challenging to understand which processes lead to an increase or decrease in drug solution concentration. Closed, nonsink dissolution testing methods used routinely, in the absence of drug removal, allow only for static equilibrium to exist and obscure the impact of each drug species on absorption. An artificial gut simulator (AGS) introduced recently consists of a hollow fiber-based absorption module and allows mass transfer of the drug from the dissolution media at a physiological rate after tuning the operating parameters. In the present work, ASDs of varying drug loadings were prepared with a BCS-II model compound, ketoconazole (KTZ), and hypromellose acetate succinate (HPMCAS) polymer. Simultaneous dissolution and absorption testing of the ASDs was conducted with the AGS, and simple analytical techniques were utilized to elucidate the impact of bound drug species on absorption. In all cases, a lower amount of crystalline precipitate was formed in the presence of absorption relative to the nonsink dissolution "control". However, formation of HPMCAS-bound drug species and crystalline precipitate significantly reduced KTZ absorption. Moreover, at high drug loading, inclusion of an absorption module was shown to enhance ASD dissolution. The rank ordering of the ASDs with respect to dissolution was significantly different when nonsink dissolution versus AGS was used, and this discrepancy could be mechanistically elucidated by understanding drug dissolution and speciation in the presence of absorption.

Simulation Guided Coaxial Electrospinning of Polyvinylidene Fluoride Hollow Fibers with Tailored Piezoelectric Performance.

Electrospun polyvinylidene fluoride (PVDF) piezoelectric fibers have high potential applicability in mechanical energy harvesting and self-powered sensing owing to their high electromechanical coupling capabilities. Strategies for tailoring fiber morphology have been the primary focus for realizing enhanced piezoelectric output. However, the relationship between piezoelectric performance and fiber structure remains unclear. This study fabricates PVDF hollow fibers through coaxial electrospinning, whose wall thickness can be tuned by changing the internal solution concentration. Simulation analysis demonstrates an increased effective deformation of the hollow fiber as enlarging inner diameter, resulting in enhanced piezoelectric output, which is in excellent agreement with the experimental results. This study is the first to unravel the influence mechanism of morphology regulation of a PVDF hollow fiber on its piezoelectric performance from both simulation and experimental aspects. The optimal PVDF hollow fiber piezoelectric energy harvester (PEH) delivers a piezoelectric output voltage of 32.6 V, ≈3 times that of the solid PVDF fiber PEH. Furthermore, the electrical output of hollow fiber PEH can be stably stored in secondary energy storage systems to power microelectronics. This study highlights an efficient approach for reconciling the simulation and tailoring the fiber PEH morphology for enhanced performances for future self-powered systems.

Enhancing Water Treatment Performance of Porous Polysulfone Hollow Fiber Membranes through Atomic Layer Deposition.

Polysulfone (PSF) is one of the most used polymers for water treatment membranes, but its intrinsic hydrophobicity can be detrimental to the membranes' performances. By modifying a membrane's surface, it is possible to adapt its physicochemical properties and thus tune the membrane's hydrophilicity or porosity, which can achieve improved permeability and antifouling efficiency. Atomic layer deposition (ALD) stands as a distinctive technology offering exceedingly even and uniform layers of coatings, like oxides that cover the surfaces of objects with three-dimensional (3D) shapes, porous structures, and particles. In the context of this study, the focus was on titanium dioxide (TiO2), zinc oxide (ZnO), and alumina (Al2O3), which were deposited on polysulfone hollow fiber (HF) membranes via ALD using TiCl4, diethyl zinc (DEZ), and trimethylamine (TMA), respectively, and H2O as precursors. The morphology and mechanical properties of membranes were changed without damaging their performances. The deposition was confirmed mainly by energy-dispersive X-ray spectroscopy (EDX). All depositions offered great performances with a maintained permeability and BSA retention and a 20 to 40° lower water contact angle (WCA) than the raw PSF HF membrane. The deposition of TiO2 offered the best results, showing an enhancement of 50% for the water permeability and 20% for the fouling resistance of the PSF HF membranes.

Preconcentration and determination of five antidepressants from human milk and urine samples by stir bar filled magnetic ionic liquids using liquid-liquid-liquid microextraction-high-performance liquid chromatography.

A sensitive and straightforward liquid-liquid-liquid microextraction method was developed to preconcentrate and cleanup antidepressants, including mirtazapine, venlafaxine, escitalopram, fluoxetine, and fluvoxamine, from biological samples before analyzing with high-performance liquid chromatography. The essential novelty of this study is using magnetic ionic liquids as the extraction phase in the lumen of hollow fiber and preparing a liquid magnetic stir bar. In this method, polypropylene hollow fiber was utilized as the permeable membrane for the analyte extraction. Six magnetic ionic liquids consisting of the transition metal and rare earth compounds were synthesized and then hollow fiber lumen was injected as acceptor phase to extract the antidepressants. Besides, 3-pentanol as a water-immiscible solvent was impregnated in the hollow fiber wall pores. The effective factors in the method were optimized with the central composition design. The resultant calibration curves were linear over the concentration range of 0.8-400.0 ng mL-1 (R2 ≥ 0.996). The method displayed the proper detection limit (0.11-0.24 ng mL-1 ), the reasonable limit of quantification (≤0.79 ng mL-1 ), wide linear ranges, high preconcentration factors (≥294.3), and suitable relative standard deviation (2.31-5.47%) for measuring antidepressant medications. Analysis of human milk and urine samples showed acceptable recoveries of 96.5-103.8% with excellent relative standard deviations lower than 5.95%.

Polymer-Based Mechanochromic Composite Material Using Encapsulated Systems.

The development of mechanochromic or self-reporting polymers that can indicate damage or fatigue of materials with an optical signal has become of paramount interest to ensure the reliability of the materials and prevent catastrophic failure. This technology can potentially find usefulness for various applications, including in situ monitoring of mechanical events and structural health monitoring systems. An emerging and versatile approach to achieve mechanochromic properties relies on the encapsulation of dye solutions that can be released and activated (chemically or physically) when the walls of the capsules are mechanically damaged. While the mechanochromic effect can be achieved with different types of dyes and operating principles, this framework can also be designed with encapsulating-containers of different shapes and shell materials, such as microcapsules, hollow glass fibers, vascular networks, and micelles, making this concept applicable to a broad range of polymer matrices. An overview of the different encapsulation approaches that have been employed to prepare mechanochromic polymers is given, with a focus on the containers used for this purpose. A brief description of the containers' preparation is provided, and their associated chromic operating principles and progress in their designs are reviewed.

Optimized process operations reduce product retention and column clogging in ATF-based perfusion cell cultures.

Product retention in hollow fibers is a common issue in ATF-based cell culture system. In this study, the effects of four major process factors on product (therapeutic antibody/recombinant protein) retention were investigated using Chinese hamster ovary cell. Hollow fibers made of polysulfone presented a product retention rate from 15% ± 8 to 43% ± 18% higher than those made of polyether sulfone varying with specific processes. Higher harvest flowrate and ATF exchange rate increased product retention by 13% ± 10% and up to 31% ± 13%, respectively. Hollow fibers with larger pore sizes (0.65 µm) appeared to have increased product retention by 38% ± 7% compared with smaller ones (0.2 µm) in this study. Further investigation revealed that the effects of pore size on retention could be correlated to the particle size distribution in the cell culture broth. A hollow fiber with a larger pore size (>0.5 µm) may reduce protein retention when small particles (approximately 0.01-0.2 µm in diameter) are dominant in the culture. However, if majority of the particles are larger than 0.2 µm in diameter, hollow fiber with smaller pore sizes (0.2 µm) could be a solution to reducing product retention. Alternatively, process optimization may modulate particle size distribution towards reduced production retention with selected ATF hollow fibers. This study for the first time highlights the importance of matching proper pore sizes of hollow fibers with the cell culture particles distribution and offers methods to reducing product retention and ATF column clogging in perfusion cell cultures. KEY POINTS: The material of ATF column could impact product retention during perfusion culture. Higher harvest flowrate and ATF exchange rate increased product retention. Matching culture particle size and ATF pore size is critical for retention modulation.

Synthesis of an organic-inorganic hybrid absorbent for in-tube solid-phase microextraction of bisphenol A.

This research is an application of fiber-in-tube solid-phase microextraction followed by high-performance liquid chromatography with UV detection for the extraction and determination of trace amounts of bisphenol A. Nanomagnetic Fe3 O4 was formed on the surface of polypropylene porous hollow fibers to increase the surface area and then it was coated with polystyrene. The introduction of polystyrene improves the surface hydrophobicity and is an appropriate extractive phase because it is highly stable in aquatic media. The extraction was carried out in a short capillary packed longitudinally with the fine fibers as the extraction medium. Extraction conditions, including extraction and desorption flow rates, extraction time, pH, and ionic strength of the sample solution, were investigated and optimized. Under optimal conditions, the limit of detection was 0.01 µg/L. This method showed good linearity for bisphenol A in the range of 0.033-1000 µg/L, with the coefficient of determination of 0.9984. The inter- and intraday precisions (RSD%, n = 3) were 7.9 and 6.3%, respectively. Finally, the method was applied to analysis of the analyte in thermal papers, disposable plastic cups, and soft drink bottles.

Al2 O3 -Assisted Confinement Synthesis of Oxide/Carbon Hollow Composite Nanofibers and Application in Metal-Ion Capacitors.

Hollow micro-/nanostructures are widely explored for energy applications due to their unique structural advantages. The synthesis of hollow structures generally involves a "top-down" casting process based on hard or soft templates. Herein, a new and generic confinement strategy is developed to fabricate composite hollow fibers. A thin and homogeneous atomic-layer-deposition (ALD) Al2 O3 layer is employed to confine the pyrolysis of precursor fibers, which transform into metal (or metal oxide)-carbon composite hollow fibers after removal of Al2 O3 . Because of the uniform coating by ALD, the resultant composite hollow fibers exhibit a hollow interior from heads to ends even if they are millimeter long. V, Fe, Co, and Ni-based hollow nanofibers, demonstrating the versatility of this synthesis method, are successfully synthesized. Because of the carbon constituent, these composite fibers are particularly useful for energy applications. Herein, the as-obtained hollow V2 O3 -C fiber membrane is employed as a freestanding and flexible electrode for lithium-ion capacitor. The device shows an impressive energy density and a high power density.

Critical evaluation of microextraction pretreatment techniques-Part 2: Membrane-supported and homogenous phase based techniques.

This review follows up on Part 1, which focused on classification and evaluation of single drop and sorbent-based microextraction techniques. Membrane- and homogenous phase-based microextraction techniques are discussed and classified in Part 2. These techniques are more recent than those in Part 1 and considerable attention has been paid to their development. The new methodologies are more sensitive and, thanks to their miniaturization, they can be classified as "green", but no exhaustive classification is available. We hope that this review will contribute to better orientation in these methods.

Bare polyprolylene hollow fiber as extractive phase for in-tube solid-phase microextraction to determine estrogens in water samples.

Polypropylene hollow fibers as the adsorbent were directly filled into a polyetheretherketone tube for in-tube solid-phase microextraction. The surface properties of hollow fibers were characterized by a scanning electron microscope. Combined with high performance liquid chromatography, the extraction tube showed good extraction performance for five environmental estrogen hormones. To achieve high analytical sensitivity, four important factors containing sampling volume, sampling rate, content of organic solvent in sample, and desorption time were investigated. Under the optimum conditions, an online analysis method was established with wide linear range (0.03-20 µg/L), good correlation coefficients (≥0.9998), low limits of detection (0.01-0.05 µg/L), low limits of quantitation (0.03-0.16 µg/L), and high enrichment factors (1087-2738). Relative standard deviations (n = 3) for intraday (≤3.6%) and interday (≤5.1%) tests proved the stable extraction performance of the material. Durability and chemical stability of the extraction tube were also investigated, relative standard deviations of all analytes were less than 5.8% (n = 3), demonstrating the satisfactory stability. Finally, the method was successfully applied to detect estrogens in real samples.

Continuous Zeolite MFI Membranes Fabricated from 2D MFI Nanosheets on Ceramic Hollow Fibers.

High-quality 2D MFI nanosheet coatings were prepared on α-alumina hollow fiber supports by vacuum filtration and then transformed into molecular sieving membranes by two sequential hydrothermal treatments. This processing method eliminates the need for specially engineered silica-based support materials that have so far been necessary to allow the formation of functional membranes from 2D MFI nanosheets. The sequential steps enhance adhesion of the membrane on the fiber support, fill in nanoscale gaps between the 2D nanosheets, and preserve the desirable (0k0) out-of-plane orientation without the need of any support engineering or modification. The membrane exhibits high performance for separation of n-butane from i-butane, and for other technologically important hydrocarbon separations. The present findings have strong implications on strategies for obtaining thin, highly selective zeolite membranes from 2D zeolites in a technologically scalable manner.

Adsorbed hollow fiber-based biological fingerprinting for the discovery of platelet aggregation inhibitors from Danshen-Honghua decoction.

For lead compound discovery from natural products, hollow fiber cell fishing with chromatographic analysis is a newly developed method. In this study, an adsorbed hollow fiber-based biological fingerprinting method was firstly developed to discover potential platelet aggregation inhibitors from Danshen-Honghua decoction. Platelets were seeded on the fiber and their survival rate was tested. Results indicated that more than 92% platelets survived during the whole operation process. Ranitidine and tirofiban were used as positive and negative control respectively to verify the reliability of the presented approach. The main variables such as amount of extract and stirring time that affect the adsorbed hollow fiber-based biological fingerprinting process were optimized, and the repeatability of this method was also investigated. Finally, 12 potential active compounds in Danshen-Honghua decoction were successfully detected using the established approach and structures for nine of them were tentatively identified by liquid chromatography with mass spectrometry analysis. In addition, the in vitro platelet aggregation inhibition test was carried out for five of the nine hit compounds, and three active components, namely, lithospermic acid, salvianolic acid A, and salvianolic acid B were confirmed. These results proved that the proposed method could be an effective approach for screening platelet inhibitors from plant extracts.

Extraction and determination of trace amounts of three anticancer pharmaceuticals in urine by three-phase hollow fiber liquid-phase microextraction based on two immiscible organic solvents followed by high-performance liquid chromatography.

An automated three-phase hollow fiber liquid-phase microextraction based on two immiscible organic solvents followed by high-performance liquid chromatography with UV-Vis detection method was applied for the extraction and determination of exemestane, letrozole, and paclitaxel in water and urine samples. n-Dodecane was selected as the supported liquid membrane and its polarity was justified by trioctylphosphine oxide. Acetonitrile was used as an organic acceptor phase with desirable immiscibility having n-dodecane. All the effective parameters of the microextraction procedure such as type of the organic acceptor phase, the supported liquid membrane composition, extraction time, pH of the donor phase, hollow fiber length, stirring rate, and ionic strength were evaluated and optimized separately by a one variable at-a-time method. Under the optimal conditions, the linear dynamic ranges were 1.8-200 (R2  = 0.9991), 0.9-200 (R2  = 0.9987) and 1.2-200 µg/L (R2  = 0.9983), and the limits of detection were 0.6, 0.3, and 0.4 µg/L for exemestane, letrozole, and paclitaxel, respectively. To evaluate the capability of the proposed method in the analysis of biological samples, three different urinary samples were analyzed under the optimal conditions. The relative recoveries of the three pharmaceuticals were in the range of 91-107.3% for these three analytes.

The art of separation and adsorption: Historical review of apheresis in Japan.

Apheresis therapy was first introduced into Japan from the United State as plasmapheresis by a centrifuge method. However, the invention of hollow fiber has subsequently lead to a membrane plasma separation. Selective removal of the plasma or cell component has been improved and matured in clinical application. Therapeutic apheresis has progressed and diversified with the development of technology for membrane separation by hollow fiber and adsorption with a physicochemical adsorbent in Japan.

Hollow fiber stir bar sorptive extraction for determination of phthalic acid esters in environmental and biological matrices.

The purpose of this paper is to introduce a novel hollow fiber stir bar sorptive extraction for collecting and determining of phthalic acid esters in environmental and biological matrices. Shell-core ZrO2 /SiO2 composite microspheres and porous C18 silica microspheres were compared as the sorbents, which were loaded in the lumen of a microporous hollow fiber membrane. A thin stainless-steel wire was also inside of the hollow fiber membrane acting as the magnetic stirrer, thus affording the procedures like stir bar sorptive extraction to perform the active trapping of the analytes. Variables affecting the extraction (salt addition and pH of samples, extraction temperature, and time) and desorption (microwave time and eluted solvents) have been optimized. Under the optimal conditions, good linearity (r > 0.9968) of all calibration curves was obtained in validation experiments. And the limits of quantification ranged from 0.01 to 1000 ng/mL. The recoveries in different matrices were in the range of 64.90-112.60% with relative standard deviations less than 8.60%. The present work demonstrated the applicability of the developed method for the determination of phthalic acid esters in environmental and biological sample, allowing the selective extraction of phthalate esters in complex samples with low consumption of organic solvents and no sample clean-up.

Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 µm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 µm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

Hollow-fiber double-solvent synergistic microextraction with high-performance liquid chromatography for the determination of antitumor alkaloids in Coptis chinensis.

A new hollow-fiber double-solvent synergistic microextraction method was proposed for the extraction and concentration of trace active compounds in traditional Chinese medicine. The main variables affecting the method were investigated and optimized. Under the optimized conditions, linearities were 0.01-10 µg/mL, detection limits were lower than 0.8 ng/mL, and interday, and intraday relative standard deviations were <9.20%. Furthermore, average recoveries ranged from 102.8 to 104.1%, and enrichment factors were 6-70 for the four alkaloids tested. The antitumor alkaloid group in Coptis chinensis was screened and identified by hollow-fiber cell fishing with high-performance liquid chromatography. The four alkaloids were then enriched and quantified by hollow-fiber double-solvent synergistic microextraction with high-performance liquid chromatography. The mechanism of the proposed microextraction method was described, and results demonstrated that the approach was a simple and reliable sample-preparation procedure. This method, as well as hollow-fiber cell fishing combined with high-performance liquid chromatography can be adopted to study the different characteristic effects of the multiple components and multiple targets of traditional Chinese medicine. The approach can also be used to conduct tailored quality control of the active compounds associated with therapeutic efficacy.

Screening and quantification of anticancer compounds in traditional Chinese medicine by hollow fiber cell fishing and hollow fiber liquid/solid-phase microextraction.

Hollow fiber cell fishing, based on HepG-2, SKOV-3, and ACHN cancer cells, and hollow fiber liquid/solid microextraction with HPLC were developed and introduced for researching the anticancer activity of Rhizoma Curcumae Longae, Radix Curcumae, and Rhizoma Curcumae. The structures of curcumin, demethoxycurcumin, and bisdemethoxycurcumin screened were identified and their contents were determined. The compound target fishing factors and cell apoptosis rates under the effect of the three medicines were determined. The binding sites (cell membrane and cell organelle) and binding target (phospholipase C) on the cell were researched. Hollow fiber liquid/solid-phase microextraction mechanism was analyzed and expounded. Before the application, cell seeding time, growth state and survival rate, compound nonspecific binding, positive and negative controls, repeatability in hollow fiber cell fishing with high-performance liquid chromatography; extraction solvent, sample pH, salt concentration, agitation speed, extraction time, temperature and sample volume in hollow fiber liquid/solid-phase microextraction with high-performance liquid chromatography were investigated. The results demonstrated that the proposed strategy is a simple and quick method to identify bioactive compounds at the cellular level as well as determine their contents (particularly trace levels of the bioactive compounds), analyze multicompound and multitarget entirety effects, and elucidate the efficacious material base in traditional medicine.

Monosaccharide composition analysis of immunomodulatory polysaccharides by on-line hollow fiber microextraction with high-performance liquid chromatography.

The monosaccharide compositions of functional polysaccharides are essential for structure elucidation and biological activity determination. A sensitive method based on on-line hollow-fiber liquid-phase microextraction with high-performance liquid chromatography has been established for the analysis of ten monosaccharide compositions (two uronic acids, two amino sugars and six neutral sugars) of the immunomodulatory polysaccharides. After derivatization, the sample was injected into the lumen of a hollow fiber immersed in butyl ether and separated by liquid chromatography. Under optimized conditions, the calibration curves were linear (r ≥ 0.9996) in the range of 10-2000 µmol L(-1) . The limits of detection were in the range of 0.04-1.58 µmol L(-1) , and the recoveries were in the range of 92.1-99.6%, which shows that the method is applicable to the analysis of the monosaccharide composition of various polysaccharides.

Fabrication of Hollow Materials by Fast Pyrolysis of Cellulose Composite Fibers with Heterogeneous Structures.

A facile method for the fabrication of inorganic hollow materials from cuprammonium cellulose composite filaments based on fast pyrolysis has been developed. Unlike Ostwald ripening, approaches based on the Kirkendall effect, and other template methods, this process yielded hollow materials within 100 s. The heterogeneous structure of the cellulose composite fibers and the gradient distribution of the metal oxides are the main reasons for the formation of the hollow structure. The diameter, wall thickness, and length of the hollow microfibers could be conveniently controlled. With their perfect morphology, these hollow structural materials have great potential for use in various fields.