The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths...The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths were documented globally.COVID-19 has been rapidly evolving,affecting virus transmissibility and properties and contributing to increased disease severity.The Omicron is themost circulating variant of concern.Although success in its treatment has indicated progress in tackling the virus,limitations in delivering the current antiviral agents in battling emerging variants remain remarkable.With the latest advancements in nanotechnology for controlling infectious diseases,liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies,incorporating monoclonal antibodies for the active and passive targeting of infected patients.This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARSCoV-2 and its variants.展开更多
Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mos...Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mostly relies on trial-and-error process with low efficiency.Here liposome formulation prediction models have been built by machine learning(ML)approaches.The important parameters of liposomes,including size,polydispersity index(PDI),zeta potential and encapsulation,are predicted individually by optimal ML algorithm,while the formulation features are also ranked to provide important guidance for formulation design.The analysis of key parameter reveals that drug molecules with logS[-3,-6],molecular complexity[500,1000]and XLogP3(≥2)are priority for preparing liposome with higher encapsulation.In addition,naproxen(NAP)and palmatine HCl(PAL)represented the insoluble and water-soluble molecules are prepared as liposome formulations to validate prediction ability.The consistency between predicted and experimental value verifies the satisfied accuracy of ML models.As the drug properties are critical for liposome particles,the molecular interactions and dynamics of NAP and PAL liposome are further investigated by coarse-grained molecular dynamics simulations.The modeling structure reveals that NAP molecules could distribute into lipid layer,while most PAL molecules aggregate in the inner aqueous phase of liposome.The completely different physical state of NAP and PAL confirms the importance of drug properties for liposome formulations.In summary,the general prediction models are built to predict liposome formulations,and the impacts of key factors are analyzed by combing ML with molecular modeling.The availability and rationality of these intelligent prediction systems have been proved in this study,which could be applied for liposome formulation development in the future.展开更多
Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiven...Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.展开更多
Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver c...Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.展开更多
[Objectives] To explore the optimal process for preparing hydroxypropyl tetrahydropyrantriol liposomes. [Methods] A refractive index method was used to determine the content of hydroxypropyl tetrahydropyrantriol. Usin...[Objectives] To explore the optimal process for preparing hydroxypropyl tetrahydropyrantriol liposomes. [Methods] A refractive index method was used to determine the content of hydroxypropyl tetrahydropyrantriol. Using particle size distribution and encapsulation rate as evaluation indicators, the effects of hydration time, ratio of organic phase to aqueous phase, granulation method, as well as thin film dispersion and reverse evaporation methods on liposomes preparation were investigated, and the optimal preparation method was selected. Single factor experiments were used to screen the drug phospholipid ratio, ultrasound time, and phospholipid cholesterol ratio, and the preparation process was optimized through orthogonal experiments. [Results] The optimal process of preparing hydroxypropyl tetrahydropyrantriol liposomes was as below: 1 : 10 of drug phospholipid ratio, 6 min of ultrasound time, 4 : 1 of phospholipid cholesterol ratio, (60.94%±7.24%) of entrapment efficiency, (86.44±6.08) nm of particle size, (0.195±0.077) of PDI. [Conclusions] The optimal preparation process of hydroxypropyl tetrahydropyrantriol liposomes selected by orthogonal experiment could effectively improve the encapsulation efficiency of hydroxypropyl tetrahydropyranotriol and reduce particle size. Moreover, the method was stable and reliable.展开更多
Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: T...Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T<sub>1/2</sub> was (19.282 ± 10.305) h, C<sub>max</sub> was (118514.828 ± 26155.134) ng/mL, AUC<sub>0-24</sub> and AUC<sub>0-∞</sub> were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT<sub>0-24</sub> and MRT<sub>0-∞</sub> were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.展开更多
Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain...Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .展开更多
To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:...Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.展开更多
The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional...The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional methods,the advantages and drawbacks of the latest techniques were reviewed.In the light of developments in many relevant areas,a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods.However,there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed.Generally speaking,due to the introduction of these latest techniques,liposome preparation is now an improved procedure.These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.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
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
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
Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which wa...Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.展开更多
The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation effici...The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation efficiency.Berberine hydrochloride liposomes were prepared in response to a transmembrane ion gradient that was established by ionophore A23187.Free and liposomal drug were separated by cation exchange resin,and then the amount of intraliposomal berberine hydrochloride was determined by UV spectrophotometry.The optimized encapsulation efficiency of berberine hydrochloride liposomes was 94.3%2.1%when the drug-to-lipid ratio was 1:20,and the mean diameter was 146.9 nm3.2 nm.As a result,the ionophore A23187-mediated ZnSO_(4)gradient method was suitable for the preparation of berberine hydrochloride liposomes that we could get the desired encapsulation efficiency and drug loading.展开更多
OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded lip...OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.展开更多
In this study, arsenic trioxide(ATO) was encapsulated in liposomes via copper acetate(Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of th...In this study, arsenic trioxide(ATO) was encapsulated in liposomes via copper acetate(Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and-21.97 ± 0.6 m V, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO–Cu complex.The in vitro drug release of ATO–Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the p H of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC0–12h and T1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%,meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)2 gradients;the co-administration of ATO and Cu(Ⅱ) via liposomal formulation may find wide applications in the treatment of various tumors.展开更多
Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposome...Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.展开更多
The potential side effects of cabazitaxel(CBZ)in the field of cancer treatment have become a great limitation to its further clinical application.Liposomal delivery is a well-established approach to increase the thera...The potential side effects of cabazitaxel(CBZ)in the field of cancer treatment have become a great limitation to its further clinical application.Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs.In this study,a PEGmodified liposome was developed for efficiently encapsulating CBZ,thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity.It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials,as it could be over 80%under the weight ratio of 20:1(total lipid:CBZ).The diameter of CBZ loaded liposome(CBZ@Lipo)was^100 nm.And the liposome suspending in aqueous medium was stable at 4°C for at least one month,according to the change of its size distribution.The killing ability of CBZ@Lipo to cancer cells was significantly lower comparing to that of CBZ solution,which could be attributed to the slow release of CBZ from the liposomes.However,CBZ@Lipo could induce an obvious apoptosis of the cancer cells at low concentration.Furthermore,CBZ@Lipo exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution.More importantly,CBZ@Lipo showed an obviously higher biosafety proved by lower hemolysis probability,stable body weight of mice during the whole experiment and no obvious lesion in histology analysis.Our work provided a useful reference of the formulation of CBZ,which had potential for greater clinical application.展开更多
基金the financial support obtained from Universiti Kebangsaan Malaysia(DIP-2021-001)ASEANIndia Science&Technology Development Fund(AISTDF)(SERB/F/3955/2022-2023).
文摘The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths were documented globally.COVID-19 has been rapidly evolving,affecting virus transmissibility and properties and contributing to increased disease severity.The Omicron is themost circulating variant of concern.Although success in its treatment has indicated progress in tackling the virus,limitations in delivering the current antiviral agents in battling emerging variants remain remarkable.With the latest advancements in nanotechnology for controlling infectious diseases,liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies,incorporating monoclonal antibodies for the active and passive targeting of infected patients.This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARSCoV-2 and its variants.
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
基金supported by the Multi-Year Research Grants from the University of Macao(MYRG2019-00032-ICMS and MYRG2020-00113-ICMS)the Macao FDCT research grant(0108/2021/A)Molecular modeling was performed at the High-Performance Computing Cluster(HPCC),which is supported by the Information and Communication Technology Office(ICTO)of the University of Macao.
文摘Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mostly relies on trial-and-error process with low efficiency.Here liposome formulation prediction models have been built by machine learning(ML)approaches.The important parameters of liposomes,including size,polydispersity index(PDI),zeta potential and encapsulation,are predicted individually by optimal ML algorithm,while the formulation features are also ranked to provide important guidance for formulation design.The analysis of key parameter reveals that drug molecules with logS[-3,-6],molecular complexity[500,1000]and XLogP3(≥2)are priority for preparing liposome with higher encapsulation.In addition,naproxen(NAP)and palmatine HCl(PAL)represented the insoluble and water-soluble molecules are prepared as liposome formulations to validate prediction ability.The consistency between predicted and experimental value verifies the satisfied accuracy of ML models.As the drug properties are critical for liposome particles,the molecular interactions and dynamics of NAP and PAL liposome are further investigated by coarse-grained molecular dynamics simulations.The modeling structure reveals that NAP molecules could distribute into lipid layer,while most PAL molecules aggregate in the inner aqueous phase of liposome.The completely different physical state of NAP and PAL confirms the importance of drug properties for liposome formulations.In summary,the general prediction models are built to predict liposome formulations,and the impacts of key factors are analyzed by combing ML with molecular modeling.The availability and rationality of these intelligent prediction systems have been proved in this study,which could be applied for liposome formulation development in the future.
基金support from the National Natural Science Foundation of China(Grants No.82304827,82074098,81841001)the Fundamental Research Funds for the Central public welfare research institutes(ZZ13-ZD-07),the National Key Research and Development Programof China(2020YFA0908000,2022YFC2303600)+7 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No:ZYYCXTD-C-202002)The Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation(B2302051)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grants No.ZZ13-YQ-108)the Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002)Supported by Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034)Supported by Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234)Supported by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(NO.SZGSP001).
文摘Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.
文摘Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.
基金Supported by Innovation and Entrepreneurship Training Program Project of Southwest Minzu University(S202210656134)Project of Sichuan Department of Science and Technology(2022NSFSC1437)Project of Sichuan Administration of Traditional Chinese Medicine(2021MS121).
文摘[Objectives] To explore the optimal process for preparing hydroxypropyl tetrahydropyrantriol liposomes. [Methods] A refractive index method was used to determine the content of hydroxypropyl tetrahydropyrantriol. Using particle size distribution and encapsulation rate as evaluation indicators, the effects of hydration time, ratio of organic phase to aqueous phase, granulation method, as well as thin film dispersion and reverse evaporation methods on liposomes preparation were investigated, and the optimal preparation method was selected. Single factor experiments were used to screen the drug phospholipid ratio, ultrasound time, and phospholipid cholesterol ratio, and the preparation process was optimized through orthogonal experiments. [Results] The optimal process of preparing hydroxypropyl tetrahydropyrantriol liposomes was as below: 1 : 10 of drug phospholipid ratio, 6 min of ultrasound time, 4 : 1 of phospholipid cholesterol ratio, (60.94%±7.24%) of entrapment efficiency, (86.44±6.08) nm of particle size, (0.195±0.077) of PDI. [Conclusions] The optimal preparation process of hydroxypropyl tetrahydropyrantriol liposomes selected by orthogonal experiment could effectively improve the encapsulation efficiency of hydroxypropyl tetrahydropyranotriol and reduce particle size. Moreover, the method was stable and reliable.
文摘Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T<sub>1/2</sub> was (19.282 ± 10.305) h, C<sub>max</sub> was (118514.828 ± 26155.134) ng/mL, AUC<sub>0-24</sub> and AUC<sub>0-∞</sub> were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT<sub>0-24</sub> and MRT<sub>0-∞</sub> were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.
文摘Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
基金supported by grants from National Natural Science Foundation of China(Grant No.81672932,81874380 and 81730108)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(Grant No.LR18H160001)+7 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LY15H160028 and LY13H130002)the Science and Technology Development Fund,Macao SAR(130/2017/A3,0099/2018/A3)Zhejiang Province Medical Science and Technology Project(Grant No.2017RC007)Key Project of Zhejiang Province Ministry of Science and Technology(Grant No.2015C03055)Talent Project of Zhejiang Association for Science and Technology(Grant No.2017YCGC002)Zhejiang Province Science and Technology Project of TCM(Grant No.2019ZZ016)Key Project of Hangzhou Ministry of Science and Technology(Grant No.20162013A07,20142013A63)Zhejiang Provincial Project for the Key Discipline of Traditional Chinese Medicine(Grant No.2017-XK-A09)。
文摘Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.
文摘The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional methods,the advantages and drawbacks of the latest techniques were reviewed.In the light of developments in many relevant areas,a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods.However,there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed.Generally speaking,due to the introduction of these latest techniques,liposome preparation is now an improved procedure.These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.
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.
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.
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.
文摘Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.
文摘The aim of the study was to prepare berberine hydrochloride long-circulating liposomes and optimize the formulation and process parameters,and investigate the influence of different factors on the encapsulation efficiency.Berberine hydrochloride liposomes were prepared in response to a transmembrane ion gradient that was established by ionophore A23187.Free and liposomal drug were separated by cation exchange resin,and then the amount of intraliposomal berberine hydrochloride was determined by UV spectrophotometry.The optimized encapsulation efficiency of berberine hydrochloride liposomes was 94.3%2.1%when the drug-to-lipid ratio was 1:20,and the mean diameter was 146.9 nm3.2 nm.As a result,the ionophore A23187-mediated ZnSO_(4)gradient method was suitable for the preparation of berberine hydrochloride liposomes that we could get the desired encapsulation efficiency and drug loading.
基金Supported by Overall Innovation Plan Projects of Science and Technology of Shaanxi Province in China(2015KTZDSF02-01-02)
文摘OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.
基金Research Grant from Liaoning Province Office of EducationChina(No.L2014395)+1 种基金the Natural Science Foundation of Liaoning Province(No.201602711)Supporting Program for Young Researchers from Sheyang Pharmaceutical University。
文摘In this study, arsenic trioxide(ATO) was encapsulated in liposomes via copper acetate(Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and-21.97 ± 0.6 m V, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO–Cu complex.The in vitro drug release of ATO–Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the p H of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC0–12h and T1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%,meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)2 gradients;the co-administration of ATO and Cu(Ⅱ) via liposomal formulation may find wide applications in the treatment of various tumors.
基金This work was supported by Research Settlement Fund for the new faculty of Seoul National University,and grants from Ministry of Science,ICT and Future Planning(No.2013035166)from Business for Cooperative R&D between Industry,Academy,and Research Institute funded Korea Small and Medium Business Administration in 2012(No.C0010962).
文摘Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.
基金supported by the National Key R&D Program of China(No.2017YFE0102200)the Natural Science Foundation of China(81373348 and 81573365)Basic Public Welfare Re-search Project of Zhejiang Province,China(LGF18H300004)
文摘The potential side effects of cabazitaxel(CBZ)in the field of cancer treatment have become a great limitation to its further clinical application.Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs.In this study,a PEGmodified liposome was developed for efficiently encapsulating CBZ,thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity.It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials,as it could be over 80%under the weight ratio of 20:1(total lipid:CBZ).The diameter of CBZ loaded liposome(CBZ@Lipo)was^100 nm.And the liposome suspending in aqueous medium was stable at 4°C for at least one month,according to the change of its size distribution.The killing ability of CBZ@Lipo to cancer cells was significantly lower comparing to that of CBZ solution,which could be attributed to the slow release of CBZ from the liposomes.However,CBZ@Lipo could induce an obvious apoptosis of the cancer cells at low concentration.Furthermore,CBZ@Lipo exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution.More importantly,CBZ@Lipo showed an obviously higher biosafety proved by lower hemolysis probability,stable body weight of mice during the whole experiment and no obvious lesion in histology analysis.Our work provided a useful reference of the formulation of CBZ,which had potential for greater clinical application.
