The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to dia...The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to diagnostic ultrasound(US)of 2 MHz.Herein,we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery(MCA).Via intravenous(i.v.)administration,the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation,leading to enhanced thrombolysis efficiency of the nUK,evidenced from smaller infarct volume and better clinical scores when compared to the i.v.dose of free uPA no matter with or without US intervention.Meanwhile,the preservation ability of the nanogels not only prolonged the circulation duration of the protein,but also resulted in the better blood-brain barrier protection of the nUK formulation,showing no increased risk on the hemorrhagic transformation than the controls.This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.展开更多
The characterization and enhanced oil recovery mechanisms of a nanosized polymeric cross-linked gel are presented herein.A negatively charged nanogel was synthesized using a typical free radical suspension polymerizat...The characterization and enhanced oil recovery mechanisms of a nanosized polymeric cross-linked gel are presented herein.A negatively charged nanogel was synthesized using a typical free radical suspension polymerization process by employing 2-acrylamido 2-methyl propane sulfonic acid monomer.The synthesized nanogel showed a narrow size distribution with one peak pointing to a predominant homogeneous droplet size.The charged nanogels were also able to adsorb at the oil-water interfaces to reduce interfacial tension and stabilize oil-in-water emulsions,which ultimately improved the recovered oil from hydrocarbon reservoirs.In addition,a fixed concentration of negatively charged surfactant(sodium dodecyl sulfate or SDS)was combined with different concentrations of the nanogel.The effect of the nanogels combined with surfactant on sandstone core plugs was examined by running a series of core flooding experiments using multiple flow patterns.The results show that combining nanogel and SDS was able to reduce the interfacial tension to a value of 6 Nm/m.The core flooding experiments suggest the ability of the nanogel,both alone and combined with SDS,to improve the oil recovery by a factor of 15%after initial seawater flooding.展开更多
In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence ima...In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.展开更多
Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and he...Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.展开更多
Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relie...Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relieving pain, promoting blood circulation, removing blood stasis, and softening hardness to dissipate stagnation, and show definite curative effect in preventing and treating breast diseases. Nano-composite hydrogels have the advantages of small toxic and side effects, high bioavailability, high targeting and controllable drug release. Therefore, this paper summarized and analyzed relevant literature of Zhuang medicine in treating breast diseases and clinical research of nanogels, providing new ideas and scientific basis for the treatment of mastitis with Zhuang medicine combined with nanogels.展开更多
基金This work is financially supported by the National Natural Science Foundation of China(81400941,51473169).
文摘The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to diagnostic ultrasound(US)of 2 MHz.Herein,we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery(MCA).Via intravenous(i.v.)administration,the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation,leading to enhanced thrombolysis efficiency of the nUK,evidenced from smaller infarct volume and better clinical scores when compared to the i.v.dose of free uPA no matter with or without US intervention.Meanwhile,the preservation ability of the nanogels not only prolonged the circulation duration of the protein,but also resulted in the better blood-brain barrier protection of the nUK formulation,showing no increased risk on the hemorrhagic transformation than the controls.This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.
文摘The characterization and enhanced oil recovery mechanisms of a nanosized polymeric cross-linked gel are presented herein.A negatively charged nanogel was synthesized using a typical free radical suspension polymerization process by employing 2-acrylamido 2-methyl propane sulfonic acid monomer.The synthesized nanogel showed a narrow size distribution with one peak pointing to a predominant homogeneous droplet size.The charged nanogels were also able to adsorb at the oil-water interfaces to reduce interfacial tension and stabilize oil-in-water emulsions,which ultimately improved the recovered oil from hydrocarbon reservoirs.In addition,a fixed concentration of negatively charged surfactant(sodium dodecyl sulfate or SDS)was combined with different concentrations of the nanogel.The effect of the nanogels combined with surfactant on sandstone core plugs was examined by running a series of core flooding experiments using multiple flow patterns.The results show that combining nanogel and SDS was able to reduce the interfacial tension to a value of 6 Nm/m.The core flooding experiments suggest the ability of the nanogel,both alone and combined with SDS,to improve the oil recovery by a factor of 15%after initial seawater flooding.
基金supported by the Ministry of Oceans and Fisheries,Korea(the project title:Development of marine material based near infrared fluorophore complex and diagnostic imaging instruments)by a Grant(1910070)from the National Cancer Center
文摘In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.
基金supported in part by an Ontario Research Fund-Research Excellence(ORF-RE)grant(Ontario,Canada)in partnership with Patheon by Thermo Fisher Scientific,Natural Sciences and Engineering Research Council(NSERC)of Canada Discovery Grant and Equipment Grants to Xiao Yu Wu,University of Toronto(Canada),Leslie Dan Faculty of Pharmacy Dean's Fund to Jamie Anne Lugtu-Pe,University of Toronto(Canada),Mitacs Accelerate Internship sponsored by Candoo Pharmatech Company Inc.to Xuning Zhang(Canada),NSERC CREATE ContRoL program support to Sako Mirzaie and Hao Han R.Chang(Canada),Ontario Graduate Scholarship(OGS)to Hao Han R.Chang(Canada),and Pharmaceutical Sciences graduate department scholarships to Hao Han R.Chang and Kuan Chen,University of Toronto(Canada).
文摘Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.
基金Supported by Undergraduate Training Program for Innovation and Entrepreneurship of Guangxi University of Chinese Medicine in 2023(S202310600116)。
文摘Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relieving pain, promoting blood circulation, removing blood stasis, and softening hardness to dissipate stagnation, and show definite curative effect in preventing and treating breast diseases. Nano-composite hydrogels have the advantages of small toxic and side effects, high bioavailability, high targeting and controllable drug release. Therefore, this paper summarized and analyzed relevant literature of Zhuang medicine in treating breast diseases and clinical research of nanogels, providing new ideas and scientific basis for the treatment of mastitis with Zhuang medicine combined with nanogels.
