The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) ...The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.展开更多
An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug e...An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosy...The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.展开更多
In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a func...In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.展开更多
Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer...Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer solution or polymer melt. Significant progress has been made in this process throughout the past few years and electrospinning has advanced its ap-plications in many fields, including pharmaceu-tics. Electrospun nanofibers show great prom-ise for developing many types of novel drug delivery systems (DDS) due to their special characteristics and the simple but useful and effective top-down fabricating process. The current state of electrospun nanofiber-based DDS is focused on drug-loaded nanofiber preparation from pharmaceutical and biode-gradable polymers and different types of DDS. However, there are more opportunities to be exploited from the electrospinning process and the corresponding drug-loaded nanofibers for drug delivery. Additionally, some other related challenges and the possible resolutions are outlined in this review.展开更多
Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th...Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.展开更多
In the paper, the in vitro dissolution of borneol in 12 hours from 6 batches of optimized inhalant samples were investigated. As a new dosage form, the in vitro release apparatus of nasal inhalant was invented and a p...In the paper, the in vitro dissolution of borneol in 12 hours from 6 batches of optimized inhalant samples were investigated. As a new dosage form, the in vitro release apparatus of nasal inhalant was invented and a pushing bump was used according to the simulation of the nose expiration and inspiration. Based on the data of r2 in the profile and similar factor f2 from 6 linear release tendencies, a good controlled release and a zero order tendency were observed. It can be suggested that there is a good correlation between the in vitro controlled release and the nose steady self-controllable expiration and inspiration, which will contribute to the trend of insoluble volatile drug controlled release and the effect of quick absorption in nasal pulmonary delivery to cure severe or acute cardiovascular or lung diseases at patients' sleeping, such as angina or breathing obstruction. Also, it was concluded that the prescription composed of insoluble volatile drugs can be prepared to be nasal inhalant from which drugs can be absorbed through nose steady self-controllable inspiration to the lung then into the blood and have a great effectiveness improvement of bioavailability at night timing drug delivery system.展开更多
pH-responsive-chitosan nanoparticles for the control release of protein drug were prepared by combining two-step crosslinking method, in which chitosan was subsequently crosslinked by sodium tripolyphosphate (TPP) a...pH-responsive-chitosan nanoparticles for the control release of protein drug were prepared by combining two-step crosslinking method, in which chitosan was subsequently crosslinked by sodium tripolyphosphate (TPP) and glycidoxypropyltrimethoxysilane (GPTMS). Compared with TPP crosslinked chitosan particles, the two-step crosslinked nanoparticles were not only pH-responsive but also more stable in wide pH range. Fluorescein isothiocyanate (FITC) labeled anti-human-IgG antibody was used as a model protein drug for evaluating the control release profile of the nano-carrier. The amount of released antibody increased from 5.6% to 50% when the pH of solution shifted from 7.4 to 6.0. The results suggest the possible application of the nanoparticles as pH- responsive drug delivery materials.展开更多
Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinat...Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinate(CHEMS) to increase the accumulation of the drug in the tumor site. To begin, we used a high-performance liquid chromatography(HPLC)method to determine the content of PTX and the encapsulation efficiency. Then, we prepared paclitaxel-loaded acid-sensitive liposomes(PTX ASLs) by a thin-film dispersion method.We investigated the physical and chemical properties of the liposomes. The particle size was 210.8 nm, the polydispersity index(PDI) was 0.182 and the ζ-potential was-31.2 mV.The liposome shape was observed by transmission electron microscopy(TEM), and the results showed that the liposomes were round with a homogenous size distribution. The release characteristics of the liposomes in vitro were studied via a dynamic dialysis method. The results showed that the prepared liposomes had acid sensitivity and sustained release properties. An in vitro cellular uptake assay of MCF-7 cells showed that the cell uptake of coumarin-6-loaded acid-sensitive liposomes was significantly higher than that of free coumarin-6. The cytotoxicity of the PTX ASLs was significantly higher than that of paclitaxel. In conclusion,these results showed that the prepared liposomes had clear acid-sensitive release characteristics and a higher cell uptake rate and cytotoxicity than free PTX. The system is very suitable for targeted cancer therapy with paclitaxel.展开更多
Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular m...Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas.With the introduction of several additional functionalities,the properties of these smart DDSs including size,surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting,and eventually achieve desired drug release for an optimized therapeutic efficiency.This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery.Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli,including pH,glutathione,adenosine-triphosphate,reactive oxygen species,enzyme and inflammatory factors are summarized.Special emphasis of this review is placed on their responsive mechanisms,drug loading models,drawbacks and merits.Several typical multi-stimuli responsive DDSs are listed.And the main challenges and potential future development are discussed.展开更多
Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stabili...Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stability,low bioavailability and possible adverse effects.Besides,kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys.These problems limit the development of pharmacological therapy for AKI.Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI,which may solve the pharmacological therapy dilemma.More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs,increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants.Here,we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.展开更多
In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of ...In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.展开更多
Water-soluble three-dimensional porous supramolecular organic frameworks(SOFs) have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery...Water-soluble three-dimensional porous supramolecular organic frameworks(SOFs) have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems(sof-DDSs) can adsorb dianionic pemetrexed(PMX),a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems展开更多
Atrazine is the second mostly used herbicide in USA,but low utilization ratio causes severe environmental problem,so controlled release system is highly needed in order to minimize the negative impact on environment.I...Atrazine is the second mostly used herbicide in USA,but low utilization ratio causes severe environmental problem,so controlled release system is highly needed in order to minimize the negative impact on environment.In this paper,a herbicide delivery system,atrazine-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPs)were prepared by forming an oilin-water emulsion using the emulsion-solvent evaporation method.By varying the preparation conditions of PLGA-NPs,such as sonication time,surfactant content,solvent fraction,and polymer content,the particle sizes of the PLGA-NPs were well controlled from 204 to 520 nm.The morphology and size distribution of PLGA-NPs were evaluated using dynamic light scattering(DLS)and scanning electron microscopy(SEM).Both the encapsulation efficiency and release profile of the herbicide from the PLGA-NPs were typically evaluated by using 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine(atrazine,ATZ)as the model.ATZ encapsulation efficiency within the PLGA-NPs was ranged from 31.6 to 50.5%.The release profiles of ATZ-loaded PLGA-NPs exhibited a much slower release rate in comparison with that of pure herbicide.The results demonstrated that the prepared PLGA-NPs had a high encapsulation efficiency and slow release rate,which could be used as a promising herbicide release system in agriculture to diminish the impact on the environment and minimize the potential harm to the farmers.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints....Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.展开更多
Continuous delivery of local anesthetics might be useful for management of localized and chronic pain. Controlled release injectable anesthetics have been developed but they can deliver the drug for only few days and ...Continuous delivery of local anesthetics might be useful for management of localized and chronic pain. Controlled release injectable anesthetics have been developed but they can deliver the drug for only few days and the release is not zero-order. A drug delivery system (DDS) consisting of a perforated reservoir for drug containment and release and its potential for management of chronic pain is described. Proof of principle is detailed for long-term zero order delivery of butamben. In this study, the DDS was a polyimide tube with a 0.20 mm hole and butamben release was evaluated in vitro. It is envisioned that the DDS could be implanted in proximity to a nerve, enervating the pain source, for long-term control of chronic pain.展开更多
In this study,using a spontaneous emulsification/solvent extraction method,BCNU-loaded PLA nanoparticles (NPs) with small particle size and narrow size distribution have been acquired. The particle size of the NPs ran...In this study,using a spontaneous emulsification/solvent extraction method,BCNU-loaded PLA nanoparticles (NPs) with small particle size and narrow size distribution have been acquired. The particle size of the NPs ranged from 40~60 nm and 100~200 nm according to different requirements. SEM and TEM showed that the particle size considerably decreases with increasing emulsification concentration and decreasing PLA concentration and ratio of oil to water. The highest drug loading ratio and drug encapsulation efficiency of NPs were 5.63% and 33.45%. The results demonstrated that decrease of initial BCNU content resulted in a noticeably increased encapsulation yield. A thorough study in vitro showed that the drug could be steadily released from NPs for one week. In addition,drug-loaded NPs had higher antitumor activity,compared with free BCNU,and sustained drug release characteristics as well.展开更多
Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular c...Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.展开更多
Four water-soluble porous supramolecular organic framework drug delivery systems(sof-DDSs) have been used to adsorb doxorubicin(DOX) in water at physiological pH of 7.4,which is driven exclusively by hydrophobicit...Four water-soluble porous supramolecular organic framework drug delivery systems(sof-DDSs) have been used to adsorb doxorubicin(DOX) in water at physiological pH of 7.4,which is driven exclusively by hydrophobicity.The resulting complexes DOX@SOFs are formed instantaneously upon dissolving the components in water.The drug-adsorbed sof-DDSs can undergo plasm circulation with important maintenance of the drug and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells.DOX is released readily in the cancer cells due to the protonation of its amino group in the acidic medium of cancer cells.In vitro and in vivo experiments reveal that the delivery of SOF-a-d remarkably improve the cytotoxicity of DOX for the MCF-7/Adr cells and tumors,leading to 13-19-fold reduction of the 1C_(50)values as compared with that of DOX.This new sof-DDSs strategy omits the indispensable loading process required by most of reported nano-scaled carriers for neutral hydrophobic chemotherapeutic agents,and thus should be highly valuable for future development of low-cost delivery systems.展开更多
基金supported by the National Natural Science Foundation of China(81771006)。
文摘The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.
文摘An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.
基金supported by the Chinese Natural Science Foundation Project (Grant No. 30970784 and 81171455)a National Distinguished Young Scholars Grant (Grant No. 31225009) from the National Natural Science Foundation of China+5 种基金the National Key Basic Research Program of China (Grant No. 2009CB930200)the Chinese Academy of Sciences (CAS) ‘Hundred Talents Program’ (Grant No. 07165111ZX)the CAS Knowledge Innovation Program, and the State HighTech Development Plan (Grant No. 2012AA020804)the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (Grant No. XDA09030301)NIH/NIMHD 8 G12 MD007597USAMRMC W81XWH-10-1-0767 grants
文摘In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.
文摘Electrospinning is a very simple and versatile process by which polymer nanofibers with di-ameters ranging from a few nanometers to sev-eral micrometers can be produced using an electrostatically driven jet of polymer solution or polymer melt. Significant progress has been made in this process throughout the past few years and electrospinning has advanced its ap-plications in many fields, including pharmaceu-tics. Electrospun nanofibers show great prom-ise for developing many types of novel drug delivery systems (DDS) due to their special characteristics and the simple but useful and effective top-down fabricating process. The current state of electrospun nanofiber-based DDS is focused on drug-loaded nanofiber preparation from pharmaceutical and biode-gradable polymers and different types of DDS. However, there are more opportunities to be exploited from the electrospinning process and the corresponding drug-loaded nanofibers for drug delivery. Additionally, some other related challenges and the possible resolutions are outlined in this review.
基金supported by the National Natural Science Foundation of China(52073145 and 82004081)the Jiangsu Talent Professor Program,Jiangsu Innovation Project of Graduate Student(KYCX23-2192)+1 种基金the National Natural Science Foundation of Nanjing University of Chinese Medicine(NZY82004081)the Special Grants of China Postdoctoral Science Foundation(2021T140792).
文摘Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.
文摘In the paper, the in vitro dissolution of borneol in 12 hours from 6 batches of optimized inhalant samples were investigated. As a new dosage form, the in vitro release apparatus of nasal inhalant was invented and a pushing bump was used according to the simulation of the nose expiration and inspiration. Based on the data of r2 in the profile and similar factor f2 from 6 linear release tendencies, a good controlled release and a zero order tendency were observed. It can be suggested that there is a good correlation between the in vitro controlled release and the nose steady self-controllable expiration and inspiration, which will contribute to the trend of insoluble volatile drug controlled release and the effect of quick absorption in nasal pulmonary delivery to cure severe or acute cardiovascular or lung diseases at patients' sleeping, such as angina or breathing obstruction. Also, it was concluded that the prescription composed of insoluble volatile drugs can be prepared to be nasal inhalant from which drugs can be absorbed through nose steady self-controllable inspiration to the lung then into the blood and have a great effectiveness improvement of bioavailability at night timing drug delivery system.
文摘pH-responsive-chitosan nanoparticles for the control release of protein drug were prepared by combining two-step crosslinking method, in which chitosan was subsequently crosslinked by sodium tripolyphosphate (TPP) and glycidoxypropyltrimethoxysilane (GPTMS). Compared with TPP crosslinked chitosan particles, the two-step crosslinked nanoparticles were not only pH-responsive but also more stable in wide pH range. Fluorescein isothiocyanate (FITC) labeled anti-human-IgG antibody was used as a model protein drug for evaluating the control release profile of the nano-carrier. The amount of released antibody increased from 5.6% to 50% when the pH of solution shifted from 7.4 to 6.0. The results suggest the possible application of the nanoparticles as pH- responsive drug delivery materials.
文摘Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinate(CHEMS) to increase the accumulation of the drug in the tumor site. To begin, we used a high-performance liquid chromatography(HPLC)method to determine the content of PTX and the encapsulation efficiency. Then, we prepared paclitaxel-loaded acid-sensitive liposomes(PTX ASLs) by a thin-film dispersion method.We investigated the physical and chemical properties of the liposomes. The particle size was 210.8 nm, the polydispersity index(PDI) was 0.182 and the ζ-potential was-31.2 mV.The liposome shape was observed by transmission electron microscopy(TEM), and the results showed that the liposomes were round with a homogenous size distribution. The release characteristics of the liposomes in vitro were studied via a dynamic dialysis method. The results showed that the prepared liposomes had acid sensitivity and sustained release properties. An in vitro cellular uptake assay of MCF-7 cells showed that the cell uptake of coumarin-6-loaded acid-sensitive liposomes was significantly higher than that of free coumarin-6. The cytotoxicity of the PTX ASLs was significantly higher than that of paclitaxel. In conclusion,these results showed that the prepared liposomes had clear acid-sensitive release characteristics and a higher cell uptake rate and cytotoxicity than free PTX. The system is very suitable for targeted cancer therapy with paclitaxel.
基金Supported by the Huxiang Young Talent Program of Hunan Province(2018RS3005)The Project of Innovation-driven Plan in Central South University(2020CX048)+3 种基金Hunan Provincial Natural Science Foundation of China(2019JJ60071,2020JJ4680)the Shenghua Yuying Project of Central South University,the Hunan Provincial Postgraduate Research and Innovation Project(CX20190242)Postgraduate Independent Exploration and Innovation Project of Central South University(2019zzts1017,2019zzts750)the Key Research Fund of Hunan Provincial Education Department(18A211).
文摘Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas.With the introduction of several additional functionalities,the properties of these smart DDSs including size,surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting,and eventually achieve desired drug release for an optimized therapeutic efficiency.This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery.Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli,including pH,glutathione,adenosine-triphosphate,reactive oxygen species,enzyme and inflammatory factors are summarized.Special emphasis of this review is placed on their responsive mechanisms,drug loading models,drawbacks and merits.Several typical multi-stimuli responsive DDSs are listed.And the main challenges and potential future development are discussed.
基金supported by New Century 151 Talent Project of Zhejiang ProvinceJoint Institute of Lishui Hospital and Zhejiang University for nanomaterials and nanotechnology。
文摘Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stability,low bioavailability and possible adverse effects.Besides,kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys.These problems limit the development of pharmacological therapy for AKI.Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI,which may solve the pharmacological therapy dilemma.More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs,increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants.Here,we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.
基金Supported by the National Natural Science Foundation of China(No.81371667,No.31271073)
文摘In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.
基金the National Natural Science Foundation of China(Nos.21432004,21529201,and 91527301)the Ministry of Science and Technology of China(No.2013CB834501)+1 种基金the Ministry of Education of China Research Fund for the Doctoral Program and of China for financial supportsupport from the Molecular Foundry,Lawrence Berkeley National Laboratory,supported by the Office of Science,Office of Basic Energy Sciences,Scientific User Facilities Division,of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231
文摘Water-soluble three-dimensional porous supramolecular organic frameworks(SOFs) have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems(sof-DDSs) can adsorb dianionic pemetrexed(PMX),a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems
基金financial supports of the National Natural Science Foundation of China(30671347)the Commonweal Specialized Research Fund of China Agriculture(201103016)the Fujian Provincial Science Foundation,China(2012J01079)
文摘Atrazine is the second mostly used herbicide in USA,but low utilization ratio causes severe environmental problem,so controlled release system is highly needed in order to minimize the negative impact on environment.In this paper,a herbicide delivery system,atrazine-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPs)were prepared by forming an oilin-water emulsion using the emulsion-solvent evaporation method.By varying the preparation conditions of PLGA-NPs,such as sonication time,surfactant content,solvent fraction,and polymer content,the particle sizes of the PLGA-NPs were well controlled from 204 to 520 nm.The morphology and size distribution of PLGA-NPs were evaluated using dynamic light scattering(DLS)and scanning electron microscopy(SEM).Both the encapsulation efficiency and release profile of the herbicide from the PLGA-NPs were typically evaluated by using 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine(atrazine,ATZ)as the model.ATZ encapsulation efficiency within the PLGA-NPs was ranged from 31.6 to 50.5%.The release profiles of ATZ-loaded PLGA-NPs exhibited a much slower release rate in comparison with that of pure herbicide.The results demonstrated that the prepared PLGA-NPs had a high encapsulation efficiency and slow release rate,which could be used as a promising herbicide release system in agriculture to diminish the impact on the environment and minimize the potential harm to the farmers.
基金financially supported by the National Natural Science Foundation of China (Nos. 82173758, China)Sichuan major science and technology project on biotechnology and medicine (2018SZDZX0018, China)
文摘Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.
文摘Continuous delivery of local anesthetics might be useful for management of localized and chronic pain. Controlled release injectable anesthetics have been developed but they can deliver the drug for only few days and the release is not zero-order. A drug delivery system (DDS) consisting of a perforated reservoir for drug containment and release and its potential for management of chronic pain is described. Proof of principle is detailed for long-term zero order delivery of butamben. In this study, the DDS was a polyimide tube with a 0.20 mm hole and butamben release was evaluated in vitro. It is envisioned that the DDS could be implanted in proximity to a nerve, enervating the pain source, for long-term control of chronic pain.
文摘In this study,using a spontaneous emulsification/solvent extraction method,BCNU-loaded PLA nanoparticles (NPs) with small particle size and narrow size distribution have been acquired. The particle size of the NPs ranged from 40~60 nm and 100~200 nm according to different requirements. SEM and TEM showed that the particle size considerably decreases with increasing emulsification concentration and decreasing PLA concentration and ratio of oil to water. The highest drug loading ratio and drug encapsulation efficiency of NPs were 5.63% and 33.45%. The results demonstrated that decrease of initial BCNU content resulted in a noticeably increased encapsulation yield. A thorough study in vitro showed that the drug could be steadily released from NPs for one week. In addition,drug-loaded NPs had higher antitumor activity,compared with free BCNU,and sustained drug release characteristics as well.
文摘Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.
基金the National Natural Science Foundation of China (Nos.21432004,21529201,91527301)the Ministry of Science and Technology of China(No.2013CB834501)+1 种基金the Ministry of Education of China Research Fund for the Doctoral Program and of China for financial supportsupport from the Molecular Foundry,Lawrence Berkeley National Laboratory,supported by the Office of Science,Office of Basic Energy Sciences,Scientific User Facilities Division,of the U.S.Department of Energy under Contract No.DE-AC0205CH11231
文摘Four water-soluble porous supramolecular organic framework drug delivery systems(sof-DDSs) have been used to adsorb doxorubicin(DOX) in water at physiological pH of 7.4,which is driven exclusively by hydrophobicity.The resulting complexes DOX@SOFs are formed instantaneously upon dissolving the components in water.The drug-adsorbed sof-DDSs can undergo plasm circulation with important maintenance of the drug and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells.DOX is released readily in the cancer cells due to the protonation of its amino group in the acidic medium of cancer cells.In vitro and in vivo experiments reveal that the delivery of SOF-a-d remarkably improve the cytotoxicity of DOX for the MCF-7/Adr cells and tumors,leading to 13-19-fold reduction of the 1C_(50)values as compared with that of DOX.This new sof-DDSs strategy omits the indispensable loading process required by most of reported nano-scaled carriers for neutral hydrophobic chemotherapeutic agents,and thus should be highly valuable for future development of low-cost delivery systems.