Treating severe burn wounds poses significant challenges,including considerable cell loss,excessive inflammation,and a high susceptibility to bacterial infections.Ideal burn dressings should exhibit excellent antibact...Treating severe burn wounds poses significant challenges,including considerable cell loss,excessive inflammation,and a high susceptibility to bacterial infections.Ideal burn dressings should exhibit excellent antibacterial properties,anti-inflammatory effects,and promote cell proliferation.Additionally,they need facilitate painless dressing changes and be user-friendly.Herein,we synthesized a thermosensitive hydrogel by crosslinking poly(N-isopropylacrylamide-co-allyloxybenzaldehyde)(PNA)and amino-terminated Pluronic F127(APF)through a Schiffbase reaction.It exhibited reversible gelsol transition and spread-ability.By incorporating piezoelectric gold nanoparticle-modified barium titanate(Au@BaTiO3)and cas-cade antioxidant MOF-818,a nanocomposite hydrogel dressing with diverse bioactive functionalities was developed.Results demonstrated that the nanocomposite hydrogel possessed gel-sol transition properties,maintained a stable gel state within a broad temperature range,and desirable self-healing property.Au@BaTiO3 exhibited good piezoelectric properties and ROS generation upon ultrasound stimulation,while MOF-818 displayed highly efficient cascade nanozyme activity.The combination of Au@BaTiO3 and MOF-818 promoted fibroblast proliferation and migration,reduced intracellular ROS levels,and induced anti-inflammatory polarization of macrophages under ultrasound stimulation.In vitro and in vivo antibacterial results disclosed that the nanocomposite hydrogel had excellent antibacterial activity under highintensity ultrasound stimulation.When applied to infected burn wounds,the nanocomposite hydrogel can rapidly sterilize the wound upon initial high-intensity ultrasound,and then reduce inflammation and promote M2 macrophage polarization by the following low-intensity ultrasound stimulation,and thus accelerating the healing by improving granulation tissue formation,angiogenesis,and collagen deposition.展开更多
Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic dru...Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic drugs with minimal side effects[1].Recently,natural medicine has garnered significant attention due to its remarkable efficacy and limited side effects.Icariin,a naturally occurring flavonoid,exhibits excellent potential as a therapeutic agent for neurodegenerative disease[2].However,its clinical application is limited by poor water solubility,low bioavailability,and high clearance rates.Here,an aqueous formulation of icariin/hydroxypropyl-β-cyclodextrin(HP-β-CD)supramolecular inclusion complex was obtained to optimize icariin properties.Furthermore,icariin cyclodextrin supramolecular inclusion complex based thermosensitive(icariin gels)was innovated.At lower temperatures,it remained in a liquid phase with high fluidity.Upon reaching the gelation temperature,it underwent a transition to a gel phase with significantly reduced fluidity,which may be suitable for the design of an intranasal delivery system for PD treatment.The innovative approach capitalizes on the exceptional characteristics of HP-β-CD,which was utilized to synergize with nasal delivery for targeted brain delivery and with icariin for PD treatment[3,4].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
Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the prima...Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.展开更多
Novel colloidal processing using thermosensitive poly（N-isopropylacrylamide） （PNIPAM） as a coagulating agent has beendeveloped to prepare complex-shaped ceramic components. In this work, the properties of PNIPAM a...Novel colloidal processing using thermosensitive poly（N-isopropylacrylamide） （PNIPAM） as a coagulating agent has beendeveloped to prepare complex-shaped ceramic components. In this work, the properties of PNIPAM aqueous solutions and therheological behavior of ZnO suspensions with PNIPAM were investigated. The results show that the PNIPAM solutions exhibitobvious thermosensitivity and its transition temperature is around 32℃. When the temperature is above 40℃ （Tc, the criticaltransition temperature of thermosensitive suspension）, the 50% ZnO （volume fraction） suspension with 8 mg/mL PNIPAM has asharp increase in viscosity and reaches up to 11.49 Pa·s at 50℃, displaying strong elasticity. The main reasons are the increase ofeffective volume fraction attributed to precipitation of PNIPAM segments and the flocculation between ZnO powder particles. Inaddition, the maximum solid loading （volume fraction） at 20 ℃ is higher than that at 40℃, which proves that the phase transition ofPNIPAM can induce the flocculation of suspension.展开更多
Magnetic and temperature-responsive luminescent composites based on poly（N-isopropylacrylamide）,magnetic nanoparticles and Na9[EuW10O36] were fabricated. The composites were investigated by IR, UV,XRD, TGA, SEM and ...Magnetic and temperature-responsive luminescent composites based on poly（N-isopropylacrylamide）,magnetic nanoparticles and Na9[EuW10O36] were fabricated. The composites were investigated by IR, UV,XRD, TGA, SEM and TEM. The prepared nanocomposites exhibit good superparamagnetic property and thermo-responsive switchable luminescence properties. The multifunctional nanocomposites can be separated by external magnetic field. Moreover, the nanocomposites exhibit an appreciable temperature response, and the red luminescence of the nanocomposites in solution can be controlled by the temperature stimuli. The hydrogel emits strong redluminescence in solution at 25 ℃,which can be seen by naked eyes. When the external temperature is 40 ℃, the red luminescence almost disappears in solution.It is expected that the multifunctional nanoparticles have potential applications in the field of biomedicine.展开更多
In this report, a novel thermosensitive poly（N-isopropylacrylamide-co-maleic anhydride-β-cyclodextrin）/（TiO2-multi-wal,led carbon nanotubes） （poly（NIPAM-co-MAH-β-CD）/（TiO2-MWCNTs）） composite was synthesize...In this report, a novel thermosensitive poly（N-isopropylacrylamide-co-maleic anhydride-β-cyclodextrin）/（TiO2-multi-wal,led carbon nanotubes） （poly（NIPAM-co-MAH-β-CD）/（TiO2-MWCNTs）） composite was synthesized by UV light photoinitiating method. The results indicated that MAH modifiedβ-CD （MAH-β-CD） could polymerize to NIPAM by UV light irradiation in the presence of TiO2-MWCNTs composite nanoparticles. The characteristic results confirmed that the TiO2-MWCNTs composite nanoparticles were embedded evenly within the thermally responsive copolymer of NIPAM and MAH-β-CD. The effects of irradiation time and TiO2-MWCNTs concentration on the yield of the composites were investigated by keeping NIPAM to MAH-β- CD mass ratio constant. The optimal polymerization reaction conditions were a TiO2-MWCNTs concentration of 10 wt.% under UV light for the illumination of 3 h.展开更多
A feasible neuron model can be effective to estimate the mode transition in neural activities in a complex electromagnetic environment.When neurons are exposed to electromagnetic field,the continuous magnetization and...A feasible neuron model can be effective to estimate the mode transition in neural activities in a complex electromagnetic environment.When neurons are exposed to electromagnetic field,the continuous magnetization and polarization can generate nonlinear effect on the exchange and propagation of ions in the cell,and then the firing patterns can be regulated completely.The conductivity of ion channels can be affected by the temperature and the channel current is adjusted for regulating the excitability of neurons.In this paper,a phototube and a thermistor are used to the functions of neural circuit.The phototube is used to capture external illumination for energy injection,and a continuous signal source is obtained.The thermistor is used to percept the changes of temperature,and the channel current is changed to adjust the excitability of neuron.This functional neural circuit can encode the external heat(temperature)and illumination excitation,and the dynamics of neural activities is investigated in detail.The photocurrent generated in the phototube can be used as a signal source for the neural circuit,and the thermistor is used to estimate the conduction dependence on the temperature for neurons under heat effect.Bifurcation analysis and Hamilton energy are calculated to explore the mode selection.It is found that complete dynamical properties of biological neurons can be reproduced in spiking,bursting,and chaotic firing when the phototube is activated as voltage source.The functional neural circuit mainly presents spiking states when the photocurrent is handled as a stable current source.Gaussian white noise is imposed to detect the occurrence of coherence resonance.This neural circuit can provide possible guidance for investigating dynamics of neural networks and potential application in designing sensitive sensors.展开更多
Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid...Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid） and poly（N-isopropylacrylamide）-b-poly（L-lysine）. Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides （NCA）, ε-benzyloxycarbonyl-L-lysine （Lys（Z）-NCA） or γ-benzyl-L-glutamate （BLG-NCA） with amino-terminated poly（N-isopropylacrylamide） macroinitiator and the subsequent deprotection reaction. The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy. Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.展开更多
Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, ...Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.展开更多
Maize（Zea mays L.）is one of the most important cereal crops,with a global production of 1.02 billion tons in 2013（Baldaufa et al.,2016）.Heterosis is widely used to increase the productivity of maize,and the first ...Maize（Zea mays L.）is one of the most important cereal crops,with a global production of 1.02 billion tons in 2013（Baldaufa et al.,2016）.Heterosis is widely used to increase the productivity of maize,and the first commercial hybrid maize was introduced in the 1930s（Duvick,2001）.展开更多
Novel thermosensitive hydrogels based on polymerization of N-isopropyl acrylamide, Sodium acrylate, and diacetone acrylamide were synthesized. The swelling ratio and dynamic swelling were investigated. The results ind...Novel thermosensitive hydrogels based on polymerization of N-isopropyl acrylamide, Sodium acrylate, and diacetone acrylamide were synthesized. The swelling ratio and dynamic swelling were investigated. The results indicated that the hydrogels exhibited high water uptake and themosensitivity. The swelling properties and volume phase transition temperature could be adjusted by contents of the comonomers in the gels.展开更多
Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, hut cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydro...Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, hut cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhe-sion stage. Moreover, seeded cells were distributed throughout the material.展开更多
The thermosensitive micellization of dextran-g-PNIPAAm in aqueous solutions has been investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscope. The formed polymeric micel...The thermosensitive micellization of dextran-g-PNIPAAm in aqueous solutions has been investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscope. The formed polymeric micelles showed different diameters of about 20 nm or 100 nm, when the solution temperature was below or above the phase transition temperature.展开更多
In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes(LTSL) containing conjugated linoleic acid-paclitaxel(CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular ...In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes(LTSL) containing conjugated linoleic acid-paclitaxel(CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular uptake and in vitro cytotoxicity of iRGD-LTSL-CLA-PTX were evaluated in B16-F10 melanoma cells. The in vivo anti-tumor effect of i RGD-LTSL-CLA-PTX was investigated using B16-F10 tumor-bearing C57BL/6 mice. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-LTSL-CLA-PTX-treated groups was 2.05-, 3.31-or 4.83-fold compared with that in the SSL-CLA-PTX group after a 2-, 4-or 6-h incubation at 42 °C, respectively. The in vivo antitumor results showed that iRGD-LTSL-CLA-PTX/heat significantly inhibited the growth of B16-F10 tumors compared with the CLA-PTX solution(LTSL-CLA-PTX, LTSL-CLA-PTX/heat and iRGD-LTSL-CLA-PTX)(P<0.01). In conclusion, the antitumor effect of iRGD-LTSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo, which was induced by both the effect of iRGD and LTSL.展开更多
A Novel thermosensitive dendritic copolymer based on polyethylene glycol（PEG） and poly（Nisopropylacrylamide）（PNIPAm） with a cloud point（CP） around 36 ？C was successfully synthesized by preparation of a dendri...A Novel thermosensitive dendritic copolymer based on polyethylene glycol（PEG） and poly（Nisopropylacrylamide）（PNIPAm） with a cloud point（CP） around 36 ？C was successfully synthesized by preparation of a dendritic polyol and followed by atom transfer radical polymerization（ATRP） of N-isopropylacrylamide. The dendritic copolymer was characterized using gel-permeation chromatography（GPC）, FTIR and 1H-NMR spectroscopy. The selfassociation behavior of the copolymer in aqueous medium was investigated by dynamic light scattering（DLS） and transmission electron microscopy（TEM）. These investigations confirmed that the dendritic copolymer showed different association behaviors at various temperatures.展开更多
Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable...Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.展开更多
The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)...The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)are able to increase the solubility of DTX inwater,and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels.The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles)can accelerate the formation of a depot of this drug-loaded system at the siteof administration.Therefore,the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection.An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety.In conclusion,theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem,with higher tumor inhibition effects and are less toxic to normal tissues.展开更多
基金the National Key Re-search and Development Project of China(No.2023YFC2412600)National Natural Science Foundation of China(Nos.52003216,82272155, 52403168)+3 种基金the Youth Project of Shaanxi Provin-cial Department of Science and Technology(Nos.2024JC-YBQN-0368,2024JC-YBQN-04502024JC-YBQN-0202)the High-Level Talents Program of Xi’an University of Science and Technology(No.2050122015)the China Postdoctoral Science Foundation(Nos.2022M712506,2024T170717).
文摘Treating severe burn wounds poses significant challenges,including considerable cell loss,excessive inflammation,and a high susceptibility to bacterial infections.Ideal burn dressings should exhibit excellent antibacterial properties,anti-inflammatory effects,and promote cell proliferation.Additionally,they need facilitate painless dressing changes and be user-friendly.Herein,we synthesized a thermosensitive hydrogel by crosslinking poly(N-isopropylacrylamide-co-allyloxybenzaldehyde)(PNA)and amino-terminated Pluronic F127(APF)through a Schiffbase reaction.It exhibited reversible gelsol transition and spread-ability.By incorporating piezoelectric gold nanoparticle-modified barium titanate(Au@BaTiO3)and cas-cade antioxidant MOF-818,a nanocomposite hydrogel dressing with diverse bioactive functionalities was developed.Results demonstrated that the nanocomposite hydrogel possessed gel-sol transition properties,maintained a stable gel state within a broad temperature range,and desirable self-healing property.Au@BaTiO3 exhibited good piezoelectric properties and ROS generation upon ultrasound stimulation,while MOF-818 displayed highly efficient cascade nanozyme activity.The combination of Au@BaTiO3 and MOF-818 promoted fibroblast proliferation and migration,reduced intracellular ROS levels,and induced anti-inflammatory polarization of macrophages under ultrasound stimulation.In vitro and in vivo antibacterial results disclosed that the nanocomposite hydrogel had excellent antibacterial activity under highintensity ultrasound stimulation.When applied to infected burn wounds,the nanocomposite hydrogel can rapidly sterilize the wound upon initial high-intensity ultrasound,and then reduce inflammation and promote M2 macrophage polarization by the following low-intensity ultrasound stimulation,and thus accelerating the healing by improving granulation tissue formation,angiogenesis,and collagen deposition.
基金supported by the National Natural Science Foundation of China(Grant No.:82104399)the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,China(Grant No.:22HHZYSS00001).
文摘Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic drugs with minimal side effects[1].Recently,natural medicine has garnered significant attention due to its remarkable efficacy and limited side effects.Icariin,a naturally occurring flavonoid,exhibits excellent potential as a therapeutic agent for neurodegenerative disease[2].However,its clinical application is limited by poor water solubility,low bioavailability,and high clearance rates.Here,an aqueous formulation of icariin/hydroxypropyl-β-cyclodextrin(HP-β-CD)supramolecular inclusion complex was obtained to optimize icariin properties.Furthermore,icariin cyclodextrin supramolecular inclusion complex based thermosensitive(icariin gels)was innovated.At lower temperatures,it remained in a liquid phase with high fluidity.Upon reaching the gelation temperature,it underwent a transition to a gel phase with significantly reduced fluidity,which may be suitable for the design of an intranasal delivery system for PD treatment.The innovative approach capitalizes on the exceptional characteristics of HP-β-CD,which was utilized to synergize with nasal delivery for targeted brain delivery and with icariin for PD treatment[3,4].
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.
基金National Natural Science Foundation of China (No.31671020) for financial support
文摘Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.
基金Project(51202296)supported by the National Natural Science Foundation of ChinaProject(20120162120006)supported by the Specialized Research Fund for the Doctoral Program of Higher Education,China
文摘Novel colloidal processing using thermosensitive poly（N-isopropylacrylamide） （PNIPAM） as a coagulating agent has beendeveloped to prepare complex-shaped ceramic components. In this work, the properties of PNIPAM aqueous solutions and therheological behavior of ZnO suspensions with PNIPAM were investigated. The results show that the PNIPAM solutions exhibitobvious thermosensitivity and its transition temperature is around 32℃. When the temperature is above 40℃ （Tc, the criticaltransition temperature of thermosensitive suspension）, the 50% ZnO （volume fraction） suspension with 8 mg/mL PNIPAM has asharp increase in viscosity and reaches up to 11.49 Pa·s at 50℃, displaying strong elasticity. The main reasons are the increase ofeffective volume fraction attributed to precipitation of PNIPAM segments and the flocculation between ZnO powder particles. Inaddition, the maximum solid loading （volume fraction） at 20 ℃ is higher than that at 40℃, which proves that the phase transition ofPNIPAM can induce the flocculation of suspension.
基金supported by the National Natural Science Foundation of China(21571074)Self-Determined Research Fund of CCNU from the Colleges' Basic Research and Operation of MOE(CCNU15A02016)111 Project B17019
文摘Magnetic and temperature-responsive luminescent composites based on poly（N-isopropylacrylamide）,magnetic nanoparticles and Na9[EuW10O36] were fabricated. The composites were investigated by IR, UV,XRD, TGA, SEM and TEM. The prepared nanocomposites exhibit good superparamagnetic property and thermo-responsive switchable luminescence properties. The multifunctional nanocomposites can be separated by external magnetic field. Moreover, the nanocomposites exhibit an appreciable temperature response, and the red luminescence of the nanocomposites in solution can be controlled by the temperature stimuli. The hydrogel emits strong redluminescence in solution at 25 ℃,which can be seen by naked eyes. When the external temperature is 40 ℃, the red luminescence almost disappears in solution.It is expected that the multifunctional nanoparticles have potential applications in the field of biomedicine.
基金the financial support provided by the National Natural Science Foundation of China (No.20977013)
文摘In this report, a novel thermosensitive poly（N-isopropylacrylamide-co-maleic anhydride-β-cyclodextrin）/（TiO2-multi-wal,led carbon nanotubes） （poly（NIPAM-co-MAH-β-CD）/（TiO2-MWCNTs）） composite was synthesized by UV light photoinitiating method. The results indicated that MAH modifiedβ-CD （MAH-β-CD） could polymerize to NIPAM by UV light irradiation in the presence of TiO2-MWCNTs composite nanoparticles. The characteristic results confirmed that the TiO2-MWCNTs composite nanoparticles were embedded evenly within the thermally responsive copolymer of NIPAM and MAH-β-CD. The effects of irradiation time and TiO2-MWCNTs concentration on the yield of the composites were investigated by keeping NIPAM to MAH-β- CD mass ratio constant. The optimal polymerization reaction conditions were a TiO2-MWCNTs concentration of 10 wt.% under UV light for the illumination of 3 h.
基金Project supported by the National Natural Science Foundation of China(Grant No.11672122).
文摘A feasible neuron model can be effective to estimate the mode transition in neural activities in a complex electromagnetic environment.When neurons are exposed to electromagnetic field,the continuous magnetization and polarization can generate nonlinear effect on the exchange and propagation of ions in the cell,and then the firing patterns can be regulated completely.The conductivity of ion channels can be affected by the temperature and the channel current is adjusted for regulating the excitability of neurons.In this paper,a phototube and a thermistor are used to the functions of neural circuit.The phototube is used to capture external illumination for energy injection,and a continuous signal source is obtained.The thermistor is used to percept the changes of temperature,and the channel current is changed to adjust the excitability of neuron.This functional neural circuit can encode the external heat(temperature)and illumination excitation,and the dynamics of neural activities is investigated in detail.The photocurrent generated in the phototube can be used as a signal source for the neural circuit,and the thermistor is used to estimate the conduction dependence on the temperature for neurons under heat effect.Bifurcation analysis and Hamilton energy are calculated to explore the mode selection.It is found that complete dynamical properties of biological neurons can be reproduced in spiking,bursting,and chaotic firing when the phototube is activated as voltage source.The functional neural circuit mainly presents spiking states when the photocurrent is handled as a stable current source.Gaussian white noise is imposed to detect the occurrence of coherence resonance.This neural circuit can provide possible guidance for investigating dynamics of neural networks and potential application in designing sensitive sensors.
基金financially supported by the National Natural Science Foundation of China (Nos. 20904053, 51021003,51173184)the Ministry of Science and Technology of China (International cooperation program 2011RI0001)the Program of the Science and Technology of Changchun (No. 2010061)
文摘Polyion complex （PIC） micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers, poly（N-isopropylacrylamide）-b-poly（L-glutamic acid） and poly（N-isopropylacrylamide）-b-poly（L-lysine）. Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides （NCA）, ε-benzyloxycarbonyl-L-lysine （Lys（Z）-NCA） or γ-benzyl-L-glutamate （BLG-NCA） with amino-terminated poly（N-isopropylacrylamide） macroinitiator and the subsequent deprotection reaction. The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy. Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.
基金Supported by the National Natural Science Foundation of China （No.20576057） and Fundamental Research Foundation of Tsinghua University （JCqn2005033）.
文摘Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.
基金supported by grants from the National Natural Science Foundation of China (Nos. 31501376 and 31570369)the National Key Research and Development Program of China (No. 2016YFD0101804)the National Transgenic Science and Technology Program (No. 2016ZX08010002)
文摘Maize（Zea mays L.）is one of the most important cereal crops,with a global production of 1.02 billion tons in 2013（Baldaufa et al.,2016）.Heterosis is widely used to increase the productivity of maize,and the first commercial hybrid maize was introduced in the 1930s（Duvick,2001）.
文摘Novel thermosensitive hydrogels based on polymerization of N-isopropyl acrylamide, Sodium acrylate, and diacetone acrylamide were synthesized. The swelling ratio and dynamic swelling were investigated. The results indicated that the hydrogels exhibited high water uptake and themosensitivity. The swelling properties and volume phase transition temperature could be adjusted by contents of the comonomers in the gels.
基金supported by the National Natural Science Foundation of China,No.31071222Jilin Province Science and Technology Development Project in China,No.20080738the Frontier Interdiscipline Program of Norman Bethune Health Science Center of Jilin University in China,No.2013106023
文摘Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, hut cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhe-sion stage. Moreover, seeded cells were distributed throughout the material.
基金This project is financially supported by the National Natural Science Foundation of China （No. 20474055）.
文摘The thermosensitive micellization of dextran-g-PNIPAAm in aqueous solutions has been investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscope. The formed polymeric micelles showed different diameters of about 20 nm or 100 nm, when the solution temperature was below or above the phase transition temperature.
基金National Natural Science Foundation of China(Grant No.81172992)the National Key Research and Development Program of China(Grant No.2017YFA0205600)
文摘In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes(LTSL) containing conjugated linoleic acid-paclitaxel(CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular uptake and in vitro cytotoxicity of iRGD-LTSL-CLA-PTX were evaluated in B16-F10 melanoma cells. The in vivo anti-tumor effect of i RGD-LTSL-CLA-PTX was investigated using B16-F10 tumor-bearing C57BL/6 mice. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-LTSL-CLA-PTX-treated groups was 2.05-, 3.31-or 4.83-fold compared with that in the SSL-CLA-PTX group after a 2-, 4-or 6-h incubation at 42 °C, respectively. The in vivo antitumor results showed that iRGD-LTSL-CLA-PTX/heat significantly inhibited the growth of B16-F10 tumors compared with the CLA-PTX solution(LTSL-CLA-PTX, LTSL-CLA-PTX/heat and iRGD-LTSL-CLA-PTX)(P<0.01). In conclusion, the antitumor effect of iRGD-LTSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo, which was induced by both the effect of iRGD and LTSL.
文摘A Novel thermosensitive dendritic copolymer based on polyethylene glycol（PEG） and poly（Nisopropylacrylamide）（PNIPAm） with a cloud point（CP） around 36 ？C was successfully synthesized by preparation of a dendritic polyol and followed by atom transfer radical polymerization（ATRP） of N-isopropylacrylamide. The dendritic copolymer was characterized using gel-permeation chromatography（GPC）, FTIR and 1H-NMR spectroscopy. The selfassociation behavior of the copolymer in aqueous medium was investigated by dynamic light scattering（DLS） and transmission electron microscopy（TEM）. These investigations confirmed that the dendritic copolymer showed different association behaviors at various temperatures.
基金financially supported by the National Natural Science Foundation of China(Grants 52172276)fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)。
文摘Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.
基金financial support to the National Natural Science Foundation of China(81202480,81302723)the Natural Science Foundation of Liaoning Province(2015020749)+1 种基金the Innovative training program for college students(201710163000080)support of the Pharmacology Laboratory Centre and the Animal Centre of Shenyang Pharmaceutical University
文摘The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)are able to increase the solubility of DTX inwater,and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels.The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles)can accelerate the formation of a depot of this drug-loaded system at the siteof administration.Therefore,the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection.An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety.In conclusion,theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem,with higher tumor inhibition effects and are less toxic to normal tissues.
