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 anal...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.展开更多
In this paper, the nitration characteristic of alcohols with mixed acid for the synthesis of energetic mate-rials in a stainless steel microreactor was investigated experimentally. The nitration of iso-octanol with HN...In this paper, the nitration characteristic of alcohols with mixed acid for the synthesis of energetic mate-rials in a stainless steel microreactor was investigated experimentally. The nitration of iso-octanol with HNO3-H2SO4 mixed acid was chosen as a typical model reaction which involved fast and strong exothermic liquid-liquid heterogeneous reaction process. The influences of mixed acid composition, flow rate, organic/aqueous flow ratio and reaction temperature have been investigated. The results indicated that the reaction could be con-ducted safely and stably in the microreactor at 25-40°C, which are enhanced compared to 15°C or below for safe operating conditions in the conventional reactors. Moreover, the 98.2% conversion of iso-octanol could be obtained and no by-products were detected in all cases.展开更多
Spray drying is a typical method to produce particles in dry powder forms at industrial scale. Most spray-dried products often show a wide range of particle properties even within the same batch. At Monash University,...Spray drying is a typical method to produce particles in dry powder forms at industrial scale. Most spray-dried products often show a wide range of particle properties even within the same batch. At Monash University, we utilise a microfluidic spray drying approach to generate uniform microparticles with tightly controlled characteristics and sizes in a scalable, almost waste-flee process. The technique is useful to correlate the effects of formulation and spray drying conditions on the properties of spray-dried particles, and can be used to test new formulations for targeted applications such as encapsulation and release of active ingredients. The synthesis route can be applied to other self-assembling systems, includ- ing mesoporous, crystalline, and hierarchically structured microparticles. As spray drying is commonly used in commercial scales, the understanding of how functional particles are formed in relation to formulations and process conditions could assist in developing a cost effective, energy and material-efficient route to produce powders with better properties and ease of handling for more advanced applications such as selective adsorption and bio-separation.展开更多
Nano/micro fibers have evoked much attention of scientists and have been researched as cutting edge and hotspot in the area of fiber science in recent years due to the rapid development of various advanced manufacturi...Nano/micro fibers have evoked much attention of scientists and have been researched as cutting edge and hotspot in the area of fiber science in recent years due to the rapid development of various advanced manufacturing technologies,and the appearance of fascinating and special functions and properties,such as the enhanced mechanical strength,high surface area to volume ratio and special functionalities shown in the surface,triggered by the nano or micro-scale dimensions.In addition,these outstanding and special characteristics of the nano/micro fibers impart fiber-based materials with wide applications,such as environmental engineering,electronic and biomedical fields.This review mainly focuses on the recent development in the various nano/micro fibers fabrication strategies and corresponding applications in the biomedical fields,including tissue engineering scaffolds,drug delivery,wound healing,and biosensors.Moreover,the challenges for the fabrications and applications and future perspectives are presented.展开更多
Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this tech- nology focus on the generation of featured microparticles for improving the function of the systems. Here, we pres...Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this tech- nology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate （GelMa） cores and poly（L-lactide-co-glycolide） （PLGA） shells for syn- ergistic and sustained drug delivery applications. The mi- croparticles were fabricated by using GelMa aqueous solu- tion and PLGA oil solution as the raw materials of the mi- croflnidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride （DOX, hydrophilic） and camptothecine （CPT, hydrophobic）, could be loaded respectively. As the inner cores were poly- merized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the micropar- ticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by ma- nipulating the flow solutions during the microfluidic emulsi- fication. Because of the solid structure of the resultant mi- croparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.展开更多
Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO...Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO_(2))-lactate oxidase(LOX)composite nanozyme on microfluidic hyaluronic acid methacrylate(HAMA)microspheres via chemical bonds,achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo.The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency.Furthermore,chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement.It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells(NPCs)in vitro.In the rat degenerative intervertebral disc model caused by lactate injection,MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix(ECM)degradation as well as inflammatory damage in vivo.Altogether,this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.展开更多
Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, ...Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation(FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles,polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer(CIJM), multi-inlet vortex mixer(MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly watersoluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.展开更多
Bone is an important part of the human body structure and plays a vital role in human health.A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical...Bone is an important part of the human body structure and plays a vital role in human health.A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical research.Hydroxyapatite(HA),a bioactive ceramic material,has a similar structure and composition to bone mineralization products.In this study,we used HA as a microfluidic chip component to provide a highly bionic bone environment.HA substrates with different microchannel structures were printed by using ceramic stereolithography(SLA)technology,and the minimum trench width was 50μm.The HA substrate with microchannels was sealed by a thin polydimethylsiloxane(PDMS)layer to make a HA-PDMS microfluidic chip.Cell culture experiments demonstrated that compared with PDMS,HA was more conducive to the proliferation and osteogenic differentiation of the human foetal osteoblast cell line(hFOB).In addition,the concentration gradient of the model drug doxorubicin hydrochloride(DOX)was successfully generated on a Christmas tree structure HA-PDMS chip,and the half maximal inhibitory concentration(IC50)of DOX was determined.The findings of this study indicate that the HA-PDMS microfluidic chip has great potential in the field of high-throughput bonerelated drug screening and bone-related research.展开更多
基金financial support from the National Natural Science Foundation of China(No.81673398)
文摘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.
基金Supported by the National Natural Science Foundation of China (20490208)the National High Technology Research and Development Program of China (2007AA030206)the Open Fund of State Key Laboratory of Explosion Science and Technology,BIT (KFJJ06-1)
文摘In this paper, the nitration characteristic of alcohols with mixed acid for the synthesis of energetic mate-rials in a stainless steel microreactor was investigated experimentally. The nitration of iso-octanol with HNO3-H2SO4 mixed acid was chosen as a typical model reaction which involved fast and strong exothermic liquid-liquid heterogeneous reaction process. The influences of mixed acid composition, flow rate, organic/aqueous flow ratio and reaction temperature have been investigated. The results indicated that the reaction could be con-ducted safely and stably in the microreactor at 25-40°C, which are enhanced compared to 15°C or below for safe operating conditions in the conventional reactors. Moreover, the 98.2% conversion of iso-octanol could be obtained and no by-products were detected in all cases.
文摘Spray drying is a typical method to produce particles in dry powder forms at industrial scale. Most spray-dried products often show a wide range of particle properties even within the same batch. At Monash University, we utilise a microfluidic spray drying approach to generate uniform microparticles with tightly controlled characteristics and sizes in a scalable, almost waste-flee process. The technique is useful to correlate the effects of formulation and spray drying conditions on the properties of spray-dried particles, and can be used to test new formulations for targeted applications such as encapsulation and release of active ingredients. The synthesis route can be applied to other self-assembling systems, includ- ing mesoporous, crystalline, and hierarchically structured microparticles. As spray drying is commonly used in commercial scales, the understanding of how functional particles are formed in relation to formulations and process conditions could assist in developing a cost effective, energy and material-efficient route to produce powders with better properties and ease of handling for more advanced applications such as selective adsorption and bio-separation.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the Strategic Priority Research Program of the Chinese Academy of Science(XDA16021103)+4 种基金the National Natural Science Foundation of China(61927805,51522302,82101184)Natural Science Foundation of Guangdong Province(2020A1515110780)Shenzhen Fundamental Research Program(JCYJ20210324102809024)Shenzhen PhD Start-up Program(RCB20210609103713045)the China Postdoctoral Science Foundation funded project(2020M680120).
文摘Nano/micro fibers have evoked much attention of scientists and have been researched as cutting edge and hotspot in the area of fiber science in recent years due to the rapid development of various advanced manufacturing technologies,and the appearance of fascinating and special functions and properties,such as the enhanced mechanical strength,high surface area to volume ratio and special functionalities shown in the surface,triggered by the nano or micro-scale dimensions.In addition,these outstanding and special characteristics of the nano/micro fibers impart fiber-based materials with wide applications,such as environmental engineering,electronic and biomedical fields.This review mainly focuses on the recent development in the various nano/micro fibers fabrication strategies and corresponding applications in the biomedical fields,including tissue engineering scaffolds,drug delivery,wound healing,and biosensors.Moreover,the challenges for the fabrications and applications and future perspectives are presented.
基金supported by the National Natural Science Foundation of China (21473029 and 51522302) the NSAF Foundation of China (U1530260)+4 种基金the National Science Foundation of Jiangsu (BK20140028) the Program for New Century Excellent Talents in Universitythe Scientific Research Foundation of Southeast UniversityFoundation of Jiangsu Cancer Hospital (ZN201609)Beijing Medical Award Foundation (YJHYXKYJJ-433)
文摘Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this tech- nology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate （GelMa） cores and poly（L-lactide-co-glycolide） （PLGA） shells for syn- ergistic and sustained drug delivery applications. The mi- croparticles were fabricated by using GelMa aqueous solu- tion and PLGA oil solution as the raw materials of the mi- croflnidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride （DOX, hydrophilic） and camptothecine （CPT, hydrophobic）, could be loaded respectively. As the inner cores were poly- merized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the micropar- ticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by ma- nipulating the flow solutions during the microfluidic emulsi- fication. Because of the solid structure of the resultant mi- croparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.
基金financially supported by the National Natural Science Foundation of China(82102578,81922045,81772314 and 21604052)the National Natural Science Foundation of Chongqing(cstc2018jcyjAX0059 and cstc2018jcyjAX0797)Applied Basic Research Programs of the Science and Technology Department of Sichuan Province(2021YJ0467).
文摘Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO_(2))-lactate oxidase(LOX)composite nanozyme on microfluidic hyaluronic acid methacrylate(HAMA)microspheres via chemical bonds,achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo.The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency.Furthermore,chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement.It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells(NPCs)in vitro.In the rat degenerative intervertebral disc model caused by lactate injection,MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix(ECM)degradation as well as inflammatory damage in vivo.Altogether,this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.
基金supported by Research Committee of University of Macao (MYRG2017-00200-ICMS)Macao Science and Technology Development Fund (FDCT 0013/2018/A1)
文摘Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation(FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles,polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer(CIJM), multi-inlet vortex mixer(MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly watersoluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.
基金The authors gratefully acknowledge funding from the Shenzhen Science and Technology Program(JCYJ20170815153105076,GJHZ20180411143347603)National Natural Science Foundation of China(31770107 and 21874116)+3 种基金Science and Technology Program of Guangdong Province(2019B010941002,2017B090911008)Guangdong Natural Science Funds for Distinguished Young Scholars(2016A030306018)Science and Technology Program of Guangzhou(201804020060,202007020002)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110102001)。
文摘Bone is an important part of the human body structure and plays a vital role in human health.A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical research.Hydroxyapatite(HA),a bioactive ceramic material,has a similar structure and composition to bone mineralization products.In this study,we used HA as a microfluidic chip component to provide a highly bionic bone environment.HA substrates with different microchannel structures were printed by using ceramic stereolithography(SLA)technology,and the minimum trench width was 50μm.The HA substrate with microchannels was sealed by a thin polydimethylsiloxane(PDMS)layer to make a HA-PDMS microfluidic chip.Cell culture experiments demonstrated that compared with PDMS,HA was more conducive to the proliferation and osteogenic differentiation of the human foetal osteoblast cell line(hFOB).In addition,the concentration gradient of the model drug doxorubicin hydrochloride(DOX)was successfully generated on a Christmas tree structure HA-PDMS chip,and the half maximal inhibitory concentration(IC50)of DOX was determined.The findings of this study indicate that the HA-PDMS microfluidic chip has great potential in the field of high-throughput bonerelated drug screening and bone-related research.
