To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF S...To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD. The DSF SD was added to borate buffer solution(BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel(DSF SD/in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD/in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD/in-situ gel as a drug delivery system can improve DSF ocular permeability.展开更多
Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of ...Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.展开更多
objective:To Investigate the preparation,dissolution and release in vitro of thermosensitive in situ gel of iodine.Methods:Using orthogonal test method for screening the best prescription;Using the formula of gel accu...objective:To Investigate the preparation,dissolution and release in vitro of thermosensitive in situ gel of iodine.Methods:Using orthogonal test method for screening the best prescription;Using the formula of gel accumulative dissolution percentage=(W1-Wt)/(W1-W0)to calculate the dissolution rate of Q by membrane-free;Calculating the accumulative release rate by the standard curve.As time increases,the dissolution rate and the release rate of the gel increased significantly.Conclusion:Thermosensitive in situ gel of iodine has good sustained release effect.展开更多
Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden.Delivery of drug to particular parts of the anterior or posterior segment has been ...Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden.Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system.Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability(<5%).The designing of a novel approach for a safe,simple,and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem.Over the past decades,several novel approaches involving different strategies have been developed to improve the ocular delivery system.Among these,the ophthalmic in-situ gel has attained a great attention over the past few years.This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.展开更多
Gel treatment has been widely applied in mature oilfields to improve sweep efficiency and control water production.Correct numerical simulation is of major importance to the optimization design and prediction of a suc...Gel treatment has been widely applied in mature oilfields to improve sweep efficiency and control water production.Correct numerical simulation is of major importance to the optimization design and prediction of a successful gel treatment.However,there exist many problems in current simulation studies in published literature.This paper first presents a comprehensive review on the major factors that have been considered at different gelation stages during gel treatment,the models used in the commercial/inhouse simulators,and current numerical simulation studies on both laboratory and field scales.Then we classify the current in-situ gel numerical simulation problems as 1,deficient model problem that has published numerical model but has not been applied in simulator and application studies;2,missing model problem that does not have published quantitative model;and 3,inaccurate application problem that does not consider the major factors of gel performance,based on the reasons from some questionable results of current simulation studies.Finally,we point out the major research efforts that should be made in the future to better simulate in-situ gel treatment process.The review indicates that numerous simulation studies using commercial software packages intend to predigest the gel treatment,many of which,however,ignore important mechanisms and mislead the operation of gel treatment.In fact,a full assessment of simulating in-situ gels cannot be achieved unless the quantitative models can be qualified in terms of transport and plugging mechanisms based on the experimental results.展开更多
Quasi-solid-state lithium metal battery is a promising candidate for next generation high energy density and high safety power supply.Despite intensive efforts on electrolytes,uncontrolled interfacial reactions on lit...Quasi-solid-state lithium metal battery is a promising candidate for next generation high energy density and high safety power supply.Despite intensive efforts on electrolytes,uncontrolled interfacial reactions on lithium with electrolyte and patchy interfacial contacts still hinder its practical process.Herein,we bring in rationally designed F contained groups into polymer skeleton via in-situ gelation for the first time to establish quasi-solid-state battery.This method achieves a capacity retention of 90%after 1000 cycles at 0.5C with LiFePO_(4)cathodes.The interface constructed by polymer skeleton and reaction with–CF_(3)lead to the predicted solid electrolyte interface species with high stability.Furthermore,we optimize molecular reactivity and interface stability with regulating F contained end groups in the polymer.Comparisons on different structures reveal that high performance solid stable lithium metal batteries rely on chemical modification as well as stable polymer skeleton,which is more critical to construct robust and steady SEI with uniform lithium deposition.New approach with functional groups regulation proposes a more stable cycling process with a capacity retention of 94.2%at 0.5C and 87.6%at 1C after 1000 cycles with LiFePO_(4) cathodes,providing new insights for the practical development of quasi-solid-state lithium metal battery.展开更多
[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determin...[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.展开更多
Cervical eropion,a pathological change associated with chronic cervicitis,is a common condition that is difficult to cure.M any pa tients particularly those with mild or medium infection and those preparing for pregna...Cervical eropion,a pathological change associated with chronic cervicitis,is a common condition that is difficult to cure.M any pa tients particularly those with mild or medium infection and those preparing for pregnancy require a simple but effective medication.In this study,extracts of an empirical herbal prescription composed of six Chinese traditional drugs viz Cortex Phellodendri,Rhizoma Coptidis,Olibanum,Myrrha,borneol and catechu were formulated to facilitate intravaginal administration and improve efficacy.An extract of the first four components was formulated with borneol as a thermosensitive gel(TG)while an extract of catechu used to prepare a regular gel(CG)because of a chemical incompatibility.The optimized TG was prepared using poloxamer 407 and poloxamer 188.The CG was prepared using glycerin,carbopol and triethanolamine.The gels were characterized in vitro in terms of release of berberine(TG)and total catechins(CG)and in vivo in a rat model of cervical erosion.Trea tment by once daily application of the TG for 7 days followed by once daily application of the CG for 3 days produced a restoration of normal tissues.Gel formulation of the empirical Chinese traditional remedy appears to provide a promising treatment for cervical erosion.展开更多
Stem cell-derived exosomes(SC-EXO)was an emerging therapeutic agent in regenerative medicine.Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction(ED)treatment.However,high ...Stem cell-derived exosomes(SC-EXO)was an emerging therapeutic agent in regenerative medicine.Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction(ED)treatment.However,high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection.In this study,a Polydopamine nanoparticles(PDNPs)incorporated poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PDNPs-PELA)thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes(EXO).The hydrogels exhibited sol-gel transition at body temperature.Moreover,the in-situ polymerization of PDNPs using poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PELA)block copolymer as a template was found to be more stable dispersion in the gel system.After being encapsulated into the hydrogel,EXO shows sustained release behavior within two weeks.In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons,increase of the cavity’s pressure,thereby restoring the erectile function.In particular,since the PDNPs in thermosensitive gels have excellent photoacoustic performance,the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging.These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.展开更多
Aim To study the diffusion behaviors of drugs in thermosensitive in situ gels, and provide valuable information for designing such delivery systems. Methods A free diffusion model was used to evaluate the effects of c...Aim To study the diffusion behaviors of drugs in thermosensitive in situ gels, and provide valuable information for designing such delivery systems. Methods A free diffusion model was used to evaluate the effects of concentration, the property of drugs, as well as the gel compositions on the diffusivity of drugs. Results Drug transport through the aqueous channels of the gel followed Fickian mechanism, and no significant influence on the diffusivity was observed when the drug concentration was lowered from 5% to 0.25%. The diffusion coefficients of propranolol, timolol maleate, and salbutamol sulfate were 0.91, 1.32, and 3.30×10 -6 cm 2·s -1 , respectively. The flux of hydrophilic drug was 3.6 fold faster than that of the lipophilic one implied the latter partitioned into the hydrophobic micellar core, and consequently the diffusion was retarded. The diffusivity was decreased with increased poloxamer and sodium hyaluronate concentration, due to the distorted aqueous channels and higher microviscosity. Conclusion The result suggested that sustained release could be achieved for the thermosensitive in situ gel by incorporating lipophilic drug or increasing polymer concentration.展开更多
基金supported by Liaoning Provincial Key Labora-tory of Drug Preparation Design and Evaluation of Liaoning Provincial Education Department(LZ2014045)
文摘To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD. The DSF SD was added to borate buffer solution(BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel(DSF SD/in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD/in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD/in-situ gel as a drug delivery system can improve DSF ocular permeability.
文摘Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.
文摘objective:To Investigate the preparation,dissolution and release in vitro of thermosensitive in situ gel of iodine.Methods:Using orthogonal test method for screening the best prescription;Using the formula of gel accumulative dissolution percentage=(W1-Wt)/(W1-W0)to calculate the dissolution rate of Q by membrane-free;Calculating the accumulative release rate by the standard curve.As time increases,the dissolution rate and the release rate of the gel increased significantly.Conclusion:Thermosensitive in situ gel of iodine has good sustained release effect.
文摘Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden.Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system.Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability(<5%).The designing of a novel approach for a safe,simple,and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem.Over the past decades,several novel approaches involving different strategies have been developed to improve the ocular delivery system.Among these,the ophthalmic in-situ gel has attained a great attention over the past few years.This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.
文摘Gel treatment has been widely applied in mature oilfields to improve sweep efficiency and control water production.Correct numerical simulation is of major importance to the optimization design and prediction of a successful gel treatment.However,there exist many problems in current simulation studies in published literature.This paper first presents a comprehensive review on the major factors that have been considered at different gelation stages during gel treatment,the models used in the commercial/inhouse simulators,and current numerical simulation studies on both laboratory and field scales.Then we classify the current in-situ gel numerical simulation problems as 1,deficient model problem that has published numerical model but has not been applied in simulator and application studies;2,missing model problem that does not have published quantitative model;and 3,inaccurate application problem that does not consider the major factors of gel performance,based on the reasons from some questionable results of current simulation studies.Finally,we point out the major research efforts that should be made in the future to better simulate in-situ gel treatment process.The review indicates that numerous simulation studies using commercial software packages intend to predigest the gel treatment,many of which,however,ignore important mechanisms and mislead the operation of gel treatment.In fact,a full assessment of simulating in-situ gels cannot be achieved unless the quantitative models can be qualified in terms of transport and plugging mechanisms based on the experimental results.
基金support from the National Natural Science Foundation of China(52034011)the Fundamental Research Funds for the Science and Technology Program of Hunan Province(2019RS3002)+1 种基金the Central Universities of Central South University(Grant No.2018zzts133)Science and Technology Innovation Program of Hunan Province(2020RC2006).
文摘Quasi-solid-state lithium metal battery is a promising candidate for next generation high energy density and high safety power supply.Despite intensive efforts on electrolytes,uncontrolled interfacial reactions on lithium with electrolyte and patchy interfacial contacts still hinder its practical process.Herein,we bring in rationally designed F contained groups into polymer skeleton via in-situ gelation for the first time to establish quasi-solid-state battery.This method achieves a capacity retention of 90%after 1000 cycles at 0.5C with LiFePO_(4)cathodes.The interface constructed by polymer skeleton and reaction with–CF_(3)lead to the predicted solid electrolyte interface species with high stability.Furthermore,we optimize molecular reactivity and interface stability with regulating F contained end groups in the polymer.Comparisons on different structures reveal that high performance solid stable lithium metal batteries rely on chemical modification as well as stable polymer skeleton,which is more critical to construct robust and steady SEI with uniform lithium deposition.New approach with functional groups regulation proposes a more stable cycling process with a capacity retention of 94.2%at 0.5C and 87.6%at 1C after 1000 cycles with LiFePO_(4) cathodes,providing new insights for the practical development of quasi-solid-state lithium metal battery.
基金Supported by Special Fund for Basic Scientific Research Business in Central Universities(2019NYB31)Scientific Research Funded Project of Southwest Minzu University(2023KYZZ06N).
文摘[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.
基金This study was supported as a Key Project by the Bureau of Zhejiang Traditional Chinese Medicine,China(No.2008ZA010).
文摘Cervical eropion,a pathological change associated with chronic cervicitis,is a common condition that is difficult to cure.M any pa tients particularly those with mild or medium infection and those preparing for pregnancy require a simple but effective medication.In this study,extracts of an empirical herbal prescription composed of six Chinese traditional drugs viz Cortex Phellodendri,Rhizoma Coptidis,Olibanum,Myrrha,borneol and catechu were formulated to facilitate intravaginal administration and improve efficacy.An extract of the first four components was formulated with borneol as a thermosensitive gel(TG)while an extract of catechu used to prepare a regular gel(CG)because of a chemical incompatibility.The optimized TG was prepared using poloxamer 407 and poloxamer 188.The CG was prepared using glycerin,carbopol and triethanolamine.The gels were characterized in vitro in terms of release of berberine(TG)and total catechins(CG)and in vivo in a rat model of cervical erosion.Trea tment by once daily application of the TG for 7 days followed by once daily application of the CG for 3 days produced a restoration of normal tissues.Gel formulation of the empirical Chinese traditional remedy appears to provide a promising treatment for cervical erosion.
基金This work was financially supported by the National Natural Science Foundation of China(81700086)Shanghai Municipal Commission of Health and Family Planning Foundation(20134087).
文摘Stem cell-derived exosomes(SC-EXO)was an emerging therapeutic agent in regenerative medicine.Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction(ED)treatment.However,high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection.In this study,a Polydopamine nanoparticles(PDNPs)incorporated poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PDNPs-PELA)thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes(EXO).The hydrogels exhibited sol-gel transition at body temperature.Moreover,the in-situ polymerization of PDNPs using poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PELA)block copolymer as a template was found to be more stable dispersion in the gel system.After being encapsulated into the hydrogel,EXO shows sustained release behavior within two weeks.In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons,increase of the cavity’s pressure,thereby restoring the erectile function.In particular,since the PDNPs in thermosensitive gels have excellent photoacoustic performance,the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging.These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.
文摘Aim To study the diffusion behaviors of drugs in thermosensitive in situ gels, and provide valuable information for designing such delivery systems. Methods A free diffusion model was used to evaluate the effects of concentration, the property of drugs, as well as the gel compositions on the diffusivity of drugs. Results Drug transport through the aqueous channels of the gel followed Fickian mechanism, and no significant influence on the diffusivity was observed when the drug concentration was lowered from 5% to 0.25%. The diffusion coefficients of propranolol, timolol maleate, and salbutamol sulfate were 0.91, 1.32, and 3.30×10 -6 cm 2·s -1 , respectively. The flux of hydrophilic drug was 3.6 fold faster than that of the lipophilic one implied the latter partitioned into the hydrophobic micellar core, and consequently the diffusion was retarded. The diffusivity was decreased with increased poloxamer and sodium hyaluronate concentration, due to the distorted aqueous channels and higher microviscosity. Conclusion The result suggested that sustained release could be achieved for the thermosensitive in situ gel by incorporating lipophilic drug or increasing polymer concentration.
