Polymerization of acrylonitrile (AN) in aqueous nitric acid initiated by polypropylene-based polyamidoxime (PPAO)-thiourea (TU) combination has been investigated. The overall rate of polymerization (R_p) under the con...Polymerization of acrylonitrile (AN) in aqueous nitric acid initiated by polypropylene-based polyamidoxime (PPAO)-thiourea (TU) combination has been investigated. The overall rate of polymerization (R_p) under the conditions of [TU]/[PPAO]<0.5 molar ratio isThe molecular weights of the polymers were found to be inversely proportional to 3/2-power of nitric acid concentration and 1-power of thiourea concentration. In addition, it is independent with the concentrations of monomer and PPAO, and decreases with increasing temperature.On the basis of these experimental results, a coordination-proton transfer mechanism for the initiation was proposed and discussed.展开更多
OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent anti...OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers展开更多
Streamline-adjustment-assisted heterogeneous combination flooding is a new technology for enhanced oil recovery for post-polymer-flooded reservoirs.In this work,we first carried out a series of 2D visualization experi...Streamline-adjustment-assisted heterogeneous combination flooding is a new technology for enhanced oil recovery for post-polymer-flooded reservoirs.In this work,we first carried out a series of 2D visualization experiments for different chemical flooding scenarios after polymer flooding.Then,we explored the synergistic mechanisms of streamline-adjustment-assisted heterogeneous combination flooding for enhanced oil recovery and the contribution of each component.Test results show that for single heterogeneous combination flooding,the residual oil in the main streamline area after polymer flooding is ready to be driven,but it is difficult to be recovered in the non-main streamline area.Due to the effect of drainage and synergism,the streamline-adjustment-assisted heterogeneous combination flooding diverts the injected chemical agent from the main streamline area to the non-main streamline area,which consequently expands the active area of chemical flooding.Based on the results from the single-factor contribution of the quantitative analysis,the contribution of temporary plugging and profile control of branched preformed particle gels ranks in the first place and followed by the polymer profile control and the effect of streamline adjustment.On the contrary,the surfactant contributes the least to enhance the efficiency of oil displacement.展开更多
Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards study...Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.展开更多
Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanopartic...Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90(HSP90)inhibition at temperatures below 50℃to achieve optimal cancer therapy and avoid surrounding damage.GI@P NPs were done by co-loading Garcinia cambogia acid(GA)and photosensitizer IR783 in polymer PLG-g-mPEG to form a nanomedicine,where IR783 with excellent photoacoustic(PA)signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells,GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy,and PLG-g-mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor.After GI@P NPs were injected into the mice,we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h.Under laser irradiation,the tumor temperature of the mice could raise to about 43.5℃,and the tumor was significantly inhibited after long-term monitoring by PA imaging.As a result,gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues.The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers,especially in the biomedical field.展开更多
Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines.Here,we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in...Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines.Here,we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in combination with immune checkpoint blockade(ICB).Current cancer ICB benefits only a small subset of patients,largely due to a lack of pre-existing target cells and checkpoint targets for ICB,tumor antigenic heterogeneity,and tumor immunosuppression.Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires,upregulating immune checkpoint levels and hence sensitizing ICB,and reducing tumor immunosuppression.Chemically defined peptide vaccines are attractive,but their current therapeutic efficacy has been limited due to 1)poor vaccine delivery to immunomodulatory lymph nodes(LNs)and antigen(Ag)-presenting cells(APCs),2)poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans,3)limited adjuvant/Ag codelivery to enhance Ag immunogenicity,and 4)limited ability to overcome tumor antigenic heterogeneity.Here,we developed nanovaccines(NVs)using pH-responsive polymeric micellular nanoparticles(NPs)for the codelivery of bi-adjuvant[Toll-like receptor(TLR)7/8 agonist R848 and TLR9 agonist CpG]and peptide neoantigens(neoAgs)to draining LNs for efficient Ag presentation in a broad range of APC subsets.These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory,and remodeled the tumor immune milium with reduced tumor immunosuppression.As a result,NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme(GBM).These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy.展开更多
The reservoir heterogeneity of Suizhong 36-1 oilfield is very obvious,the average permeability reaches 2000mD.Long-term water injection development leads to serious water channeling in high permeability layers,resulti...The reservoir heterogeneity of Suizhong 36-1 oilfield is very obvious,the average permeability reaches 2000mD.Long-term water injection development leads to serious water channeling in high permeability layers,resulting in ineffective circulation of injected water and reduction of oil recovery.It is urgent to form an effective EOR method.In this paper,the oil displacement effect of different combination slugs including polymer gel,polymer microsphere and surfactant is evaluated by means of conformance control and chemical flooding.Three-layer heterogeneous 3-D plate model is used for oil displacement experiment.The experimental results show that the combination slug sequentially composed of polymer gel,polymer microspheres and surfactant have the best oil displacement effect with the oil recovery increment by 21.2% after the first water flooding.In addition,using the best slug combination for two rounds flooding,the recovery factor increased by 28.2% compared with the first water flooding.This paper provides some new insights for enhanced oil recovery in strong heterogeneity reservoir.展开更多
利用原位聚合法在玻璃微管道内制备阴离子交换型固相萃取(SPE)微柱,以NO-2 为分析对象,针对NaNO2 KI Luminol发光体系设计微流控芯片,并将SPE微柱与微流控芯片连接起来组建成带有SPE微柱的复合式微流控芯片。分析了SPE微柱对NO-2 的吸...利用原位聚合法在玻璃微管道内制备阴离子交换型固相萃取(SPE)微柱,以NO-2 为分析对象,针对NaNO2 KI Luminol发光体系设计微流控芯片,并将SPE微柱与微流控芯片连接起来组建成带有SPE微柱的复合式微流控芯片。分析了SPE微柱对NO-2 的吸附保留与富集作用,在复合式微流控芯片上,实现了NO-2的进样、分离富集和检测,通过漏点曲线和交换容量两种方法分析了SPE微柱的柱容量。为控制SPE微柱的最大进样体积提供有利保障,并实现了食品中NO-2 的在线分离富集与检测。展开更多
基金This project supported by the National Natural Science Foundation of China.
文摘Polymerization of acrylonitrile (AN) in aqueous nitric acid initiated by polypropylene-based polyamidoxime (PPAO)-thiourea (TU) combination has been investigated. The overall rate of polymerization (R_p) under the conditions of [TU]/[PPAO]<0.5 molar ratio isThe molecular weights of the polymers were found to be inversely proportional to 3/2-power of nitric acid concentration and 1-power of thiourea concentration. In addition, it is independent with the concentrations of monomer and PPAO, and decreases with increasing temperature.On the basis of these experimental results, a coordination-proton transfer mechanism for the initiation was proposed and discussed.
文摘OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers
基金financial support from the National Natural Science Foundation of China (Grant No. 51574269)the National Science Foundation for Distinguished Young Scholars of China (Grant No. 51625403)+3 种基金the Important National Science and Technology Specific Projects of China (Grant No. 2016ZX05025-003)the Fundamental Research Funds for the Central Universities (Grant No. 15CX08004A, 18CX02169A)China Postdoctoral Science Foundation (Grant No. 2017M622319)the Natural Science Foundation of Shandong Province (Grant No. ZR2018BEE004)
文摘Streamline-adjustment-assisted heterogeneous combination flooding is a new technology for enhanced oil recovery for post-polymer-flooded reservoirs.In this work,we first carried out a series of 2D visualization experiments for different chemical flooding scenarios after polymer flooding.Then,we explored the synergistic mechanisms of streamline-adjustment-assisted heterogeneous combination flooding for enhanced oil recovery and the contribution of each component.Test results show that for single heterogeneous combination flooding,the residual oil in the main streamline area after polymer flooding is ready to be driven,but it is difficult to be recovered in the non-main streamline area.Due to the effect of drainage and synergism,the streamline-adjustment-assisted heterogeneous combination flooding diverts the injected chemical agent from the main streamline area to the non-main streamline area,which consequently expands the active area of chemical flooding.Based on the results from the single-factor contribution of the quantitative analysis,the contribution of temporary plugging and profile control of branched preformed particle gels ranks in the first place and followed by the polymer profile control and the effect of streamline adjustment.On the contrary,the surfactant contributes the least to enhance the efficiency of oil displacement.
文摘Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.
基金the National Natural Science Foundation of China(Nos.52173115,52073278,51925305 and 51873208)Jilin province science and technology development program(No.20200201103JC)Foundation of Department of Education of Jilin Province of China(No.JJKH20210828KJ).
文摘Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90(HSP90)inhibition at temperatures below 50℃to achieve optimal cancer therapy and avoid surrounding damage.GI@P NPs were done by co-loading Garcinia cambogia acid(GA)and photosensitizer IR783 in polymer PLG-g-mPEG to form a nanomedicine,where IR783 with excellent photoacoustic(PA)signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells,GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy,and PLG-g-mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor.After GI@P NPs were injected into the mice,we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h.Under laser irradiation,the tumor temperature of the mice could raise to about 43.5℃,and the tumor was significantly inhibited after long-term monitoring by PA imaging.As a result,gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues.The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers,especially in the biomedical field.
基金G.Z.acknowledges funding support from NIH(R01CA266981,R01AI168684,R35GM143014,R21NS114455)DoD CDMRP Breast Cancer Breakthrough Award Level II(BC210931/P1)+3 种基金NIH-NCATS KL2 scholarship(KL2TR002648)via VCU C.Kenneth and Dianne Wright Center for Clinical and Translational Research(UL1TR002649)American Cancer Society Research Scholar Grant(RSG-22-055-01-IBCD)METAvivor Early Career Investigator Award,among others.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.T.S.and F.C.acknowledge the National Natural Science Foundation of China(52103199,82102203)Guangdong Basic and Applied Basic Research Foundation(2020A1515110811).
文摘Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines.Here,we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in combination with immune checkpoint blockade(ICB).Current cancer ICB benefits only a small subset of patients,largely due to a lack of pre-existing target cells and checkpoint targets for ICB,tumor antigenic heterogeneity,and tumor immunosuppression.Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires,upregulating immune checkpoint levels and hence sensitizing ICB,and reducing tumor immunosuppression.Chemically defined peptide vaccines are attractive,but their current therapeutic efficacy has been limited due to 1)poor vaccine delivery to immunomodulatory lymph nodes(LNs)and antigen(Ag)-presenting cells(APCs),2)poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans,3)limited adjuvant/Ag codelivery to enhance Ag immunogenicity,and 4)limited ability to overcome tumor antigenic heterogeneity.Here,we developed nanovaccines(NVs)using pH-responsive polymeric micellular nanoparticles(NPs)for the codelivery of bi-adjuvant[Toll-like receptor(TLR)7/8 agonist R848 and TLR9 agonist CpG]and peptide neoantigens(neoAgs)to draining LNs for efficient Ag presentation in a broad range of APC subsets.These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory,and remodeled the tumor immune milium with reduced tumor immunosuppression.As a result,NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme(GBM).These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy.
基金supported by Distinguished Young Scholars Fund in Sichuan(Award No.2019JDJQ0036)Fok Ying-Tong Education Foundation,China(Grant No.171043)Youth Science and Technology Innovation Team Fund of Southwest Petroleum University(Award No.2018CXTD08).
文摘The reservoir heterogeneity of Suizhong 36-1 oilfield is very obvious,the average permeability reaches 2000mD.Long-term water injection development leads to serious water channeling in high permeability layers,resulting in ineffective circulation of injected water and reduction of oil recovery.It is urgent to form an effective EOR method.In this paper,the oil displacement effect of different combination slugs including polymer gel,polymer microsphere and surfactant is evaluated by means of conformance control and chemical flooding.Three-layer heterogeneous 3-D plate model is used for oil displacement experiment.The experimental results show that the combination slug sequentially composed of polymer gel,polymer microspheres and surfactant have the best oil displacement effect with the oil recovery increment by 21.2% after the first water flooding.In addition,using the best slug combination for two rounds flooding,the recovery factor increased by 28.2% compared with the first water flooding.This paper provides some new insights for enhanced oil recovery in strong heterogeneity reservoir.
