In-situ oral delivery of therapeutic antibodies,like monoclonal antibody,for chronic inflammation treatment is the most convenient approach compared with other administration routes.Moreover,the abundant links between...In-situ oral delivery of therapeutic antibodies,like monoclonal antibody,for chronic inflammation treatment is the most convenient approach compared with other administration routes.Moreover,the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation.However,the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions.Moreover,these antibodies have short serum half-lives,thus,require to be frequently administered with high doses to be effective,leading to low patient tolerance.Here,we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier.By encapsulating antibodies in these microcapsules,antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route,achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model.Moreover,the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery,implying the restoration of micro-ecology of the intestine.These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.展开更多
Hydrogel microcapsules are powerful microreactor vessels that have attracted widespread attention and research.Among the various methods for their generation,the aqueous two-phase system(ATPS)is by far the most straig...Hydrogel microcapsules are powerful microreactor vessels that have attracted widespread attention and research.Among the various methods for their generation,the aqueous two-phase system(ATPS)is by far the most straightforward approach.However,the high viscosity of ATPS solutions significantly limits the generation throughput of hydrogel microcapsule.In this study,we developed a novel high-throughput approach for generating hydrogel microcapsules using a microfluidic bubble-triggering strategy.By integrating constant-pressure air flow with droplet microfluidics devices,we efficiently manipulated the formation of ATPS droplet through bubble-induced Rayleigh-Plateau instability,enabling the production of uniform,monodisperse microcapsules.Additionally,the droplet generation frequency in the bubble-triggering method exceeded 36 kHz.We further demonstrated the encapsulation of genetically engineered Escherichia coli strains,which acted as biosensors for arsenic ions and caprolactam,highlighting the potential of these microcapsules for biosensing applications.This advancement in hydrogel microcapsule generation offers promising implications for scalable applications in biosensing,organoid culture,and high-throughput screening.展开更多
基金support from the National Key Science and Technology Project of China(grant number 2018YFC2000500,03)National Natural Science Foundation of China 81703430 and 81803449,CAMS Innovation Fund for Medical Sciences(grant number 2019-I2M-5-045)the Natural Science Foundation of Zhejiang Province(LYY20H300003).
文摘In-situ oral delivery of therapeutic antibodies,like monoclonal antibody,for chronic inflammation treatment is the most convenient approach compared with other administration routes.Moreover,the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation.However,the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions.Moreover,these antibodies have short serum half-lives,thus,require to be frequently administered with high doses to be effective,leading to low patient tolerance.Here,we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier.By encapsulating antibodies in these microcapsules,antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route,achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model.Moreover,the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery,implying the restoration of micro-ecology of the intestine.These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.
基金sponsored by the National Key R&D Program of China(no.2023YFB3208203)the National Natural Science Foundation of China(no.62374170)the Science and Technology Commission of Shanghai Municipality(no.23J21900200).
文摘Hydrogel microcapsules are powerful microreactor vessels that have attracted widespread attention and research.Among the various methods for their generation,the aqueous two-phase system(ATPS)is by far the most straightforward approach.However,the high viscosity of ATPS solutions significantly limits the generation throughput of hydrogel microcapsule.In this study,we developed a novel high-throughput approach for generating hydrogel microcapsules using a microfluidic bubble-triggering strategy.By integrating constant-pressure air flow with droplet microfluidics devices,we efficiently manipulated the formation of ATPS droplet through bubble-induced Rayleigh-Plateau instability,enabling the production of uniform,monodisperse microcapsules.Additionally,the droplet generation frequency in the bubble-triggering method exceeded 36 kHz.We further demonstrated the encapsulation of genetically engineered Escherichia coli strains,which acted as biosensors for arsenic ions and caprolactam,highlighting the potential of these microcapsules for biosensing applications.This advancement in hydrogel microcapsule generation offers promising implications for scalable applications in biosensing,organoid culture,and high-throughput screening.
