Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,bl...Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,blood vessel walls and even internal organs.In order to achieve precise drug delivery,various delicately conceived drug release modes based on MDDS have been developed.Herein,to elucidate the design concepts of numerous reported MDDS,we have categorized them into two levels(Level-ⅠMDDS and Level-ⅡMDDS)depending on whether nanoscale and microscale carriers are integrated within the microneedles.In this work,the design strategies of MDDS,as well as the current status of their applications in targeted and intelligent drug delivery were reviewed,while their prospects and challenges for future industrialization and clinical applications were also discussed.展开更多
In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The...In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.展开更多
The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitr...The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.展开更多
Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time...Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.展开更多
The solubility data of compounds in supercritical fluids and the correlation between the experimental solubility data and predicted solubility data are crucial to the development of supercritical technologies. In the ...The solubility data of compounds in supercritical fluids and the correlation between the experimental solubility data and predicted solubility data are crucial to the development of supercritical technologies. In the present work, the solubility data of silymarin(SM) in both pure supercritical carbon dioxide(SCCO2) and SCCO2 with added cosolvent was measured at temperatures ranging from 308 to 338 K and pressures from 8 to 22 MPa. The experimental data were fit with three semi-empirical density-based models(Chrastil, Bartle and Mendez-Santiago and Teja models) and a back-propagation artificial neural networks(BPANN) model. Interaction parameters for the models were obtained and the percentage of average absolute relative deviation(AARD%) in each calculation was determined. The correlation results were in good agreement with the experimental data. A comparison among the four models revealed that the experimental solubility data were more fit with the BPANN model with AARDs ranging from 1.14% to 2.15% for silymarin in pure SCCO2 and with added cosolvent. The results provide fundamental data for designing the extraction of SM or the preparation of its particle using SCCO2 techniques.展开更多
Clinical management of atopic dermatitis(AD)is challenged by its susceptibility to recur-rence,side effects,and high costs.We found that Portulaca oleracea L.-derived nanovesicles(PDNV)exert anti-inflammatory effects ...Clinical management of atopic dermatitis(AD)is challenged by its susceptibility to recur-rence,side effects,and high costs.We found that Portulaca oleracea L.-derived nanovesicles(PDNV)exert anti-inflammatory effects by modulating macrophage M1/M2 polarization.These effects were achieved through pathways including inhibition of nuclear factor-κB(NF-κB)and stimulator of interferon genes(STING)protein expression in diseased tissues,demonstrating their potential to ameliorate AD symptoms.To increase the transdermal permeation of PDNV,dissolvable microneedles composed primar-ily of hyaluronic acid(HA)were developed as an adjunctive means of delivery.Meanwhile,polysaccha-rides of Portulaca oleracea L.,which were synergistic with PDNV,were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA.This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD.In addition,transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L.are closest to those of ferns,which may shed light on related evolutionary and plant species identification studies.展开更多
Erythrocytes(red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems(DDS) because of their features of biocompatibility,biodegradability, and long...Erythrocytes(red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems(DDS) because of their features of biocompatibility,biodegradability, and long circulating half-life. Accordingly, a 'camouflage' comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed,providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.展开更多
The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours.Ferroptosis,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse m...The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours.Ferroptosis,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse multidrug resistance.However,simultaneous delivery of the iron sources,ferroptosis inducers,drugs,and enhanced circulation carriers within matrices remains a significant challenge.Herein,we designed and fabricated a defect self-assembly of metal-organic framework(MOF)-red blood cell(RBC)membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer.Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron(III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process.The RBC membrane could camouflage the nanoplatform for longer circulation.Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione,amplify the reactive oxidative species oxidative stress,and enable remarkable anticancer properties.Our work provides an alternative strategy for overcoming multidrug resistance,which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis.This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.展开更多
基金supported by the National Natural Science Foundation of China(Grant number 82074031)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant number TP2020054)+1 种基金Shanghai Sailing Program(21YF1447400)the Program for Shanghai High-Level Local University Innovation Team(SZY20220315).
文摘Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,blood vessel walls and even internal organs.In order to achieve precise drug delivery,various delicately conceived drug release modes based on MDDS have been developed.Herein,to elucidate the design concepts of numerous reported MDDS,we have categorized them into two levels(Level-ⅠMDDS and Level-ⅡMDDS)depending on whether nanoscale and microscale carriers are integrated within the microneedles.In this work,the design strategies of MDDS,as well as the current status of their applications in targeted and intelligent drug delivery were reviewed,while their prospects and challenges for future industrialization and clinical applications were also discussed.
基金supported by the Program from Shanghai Uni-versity of Traditional Chinese Medicine(B201725)
文摘In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.
基金supported financially by the Subject Chief Scientist Program(10XD14303900)from Science and Technology Commission of Shanghai Municipalitythe Specialized Research Fund for the Doctoral Program of Higher Education of China(20123107110005).
文摘The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.
基金the National Natural Science Foundation of China(Grant No.:82074031)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant No.:TP2020054)China,and Program for Shanghai High-level Local University Innovation Team(Grant No.:SZY20220315),China.
文摘Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
基金supported financially by the Subject Chief Scientist Program (10XD14303900) from Science and Technology Commission of Shanghai Municipalitythe Special Research Fund for the Doctoral Program of Higher Education of China (20123107110005)
文摘The solubility data of compounds in supercritical fluids and the correlation between the experimental solubility data and predicted solubility data are crucial to the development of supercritical technologies. In the present work, the solubility data of silymarin(SM) in both pure supercritical carbon dioxide(SCCO2) and SCCO2 with added cosolvent was measured at temperatures ranging from 308 to 338 K and pressures from 8 to 22 MPa. The experimental data were fit with three semi-empirical density-based models(Chrastil, Bartle and Mendez-Santiago and Teja models) and a back-propagation artificial neural networks(BPANN) model. Interaction parameters for the models were obtained and the percentage of average absolute relative deviation(AARD%) in each calculation was determined. The correlation results were in good agreement with the experimental data. A comparison among the four models revealed that the experimental solubility data were more fit with the BPANN model with AARDs ranging from 1.14% to 2.15% for silymarin in pure SCCO2 and with added cosolvent. The results provide fundamental data for designing the extraction of SM or the preparation of its particle using SCCO2 techniques.
基金supported by the National Natural Science Foundation of China(No.82474197)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(No.TP2020054,China)+1 种基金Shanghai Seventh People’s Hospital Medical Institution Preparation and Innovative Chinese Medicine R&D(Open Bidding for Selecting the Best Candidates)Project(No.QYCXZY250204,China)the Program for Shanghai High-Level Local University Innovation Team(No.SZY20220315,China).
文摘Clinical management of atopic dermatitis(AD)is challenged by its susceptibility to recur-rence,side effects,and high costs.We found that Portulaca oleracea L.-derived nanovesicles(PDNV)exert anti-inflammatory effects by modulating macrophage M1/M2 polarization.These effects were achieved through pathways including inhibition of nuclear factor-κB(NF-κB)and stimulator of interferon genes(STING)protein expression in diseased tissues,demonstrating their potential to ameliorate AD symptoms.To increase the transdermal permeation of PDNV,dissolvable microneedles composed primar-ily of hyaluronic acid(HA)were developed as an adjunctive means of delivery.Meanwhile,polysaccha-rides of Portulaca oleracea L.,which were synergistic with PDNV,were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA.This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD.In addition,transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L.are closest to those of ferns,which may shed light on related evolutionary and plant species identification studies.
文摘Erythrocytes(red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems(DDS) because of their features of biocompatibility,biodegradability, and long circulating half-life. Accordingly, a 'camouflage' comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed,providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.
基金supported by China Postdoctoral Science Foundation(2020M681372)the National Natural Science Foundation of China(Grant Nos.51933002,81902756,82074279)+2 种基金Program of Shanghai Academic Research Leader(20XD1400400)the Natural Science Foundation of Shanghai(20ZR1458300)the Open Project of State Key Laboratory of Molecular Engineering of Polymers(No.K2021-19).
文摘The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours.Ferroptosis,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse multidrug resistance.However,simultaneous delivery of the iron sources,ferroptosis inducers,drugs,and enhanced circulation carriers within matrices remains a significant challenge.Herein,we designed and fabricated a defect self-assembly of metal-organic framework(MOF)-red blood cell(RBC)membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer.Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron(III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process.The RBC membrane could camouflage the nanoplatform for longer circulation.Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione,amplify the reactive oxidative species oxidative stress,and enable remarkable anticancer properties.Our work provides an alternative strategy for overcoming multidrug resistance,which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis.This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.
