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
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
[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
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
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
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
pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments ...pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.展开更多
Liposomes have been widely researched as a delivery system and there have been many manufacturing techniques used in the production of liposomal preparations,the most common being extrusion method which will be introd...Liposomes have been widely researched as a delivery system and there have been many manufacturing techniques used in the production of liposomal preparations,the most common being extrusion method which will be introduced in this paper.However because of the unique properties of liposomes and their susceptibility to chemical and physical degradation,sterilisation remains an unresolved issue in the manufacturing of liposomebased formulations.It is especially pertinent in the pharmaceutical industry where liposomes are commonly prepared for intravenous administration.Currently,filtration and aseptic manufacturing are recommended for the preparation of sterile liposomal products.Newer aseptic manufacturing techniques such as dense gas techniques have been devised to eliminate the need for terminal sterilisation.This paper will highlight the limitations of the conventional techniques that are specific to the liposome preparation under the respective sterilisation conditions specified by the 2011 British Pharmacopoeia to achieve 106 Sterility Assurance Level,as well as modifications incorporated in the newer sterilisation technologies to overcome these limitations.This paper will introduce these techniques in brief,including their advantages and limitations.展开更多
AIM To compare the capacity of newly developed epidermal growth factor receptor(EGFR)-targeted immune magnetic liposomes(EILs) vs epithelial cell adhesion molecule(Ep CAM) immunomagnetic beads to capture colorectal ci...AIM To compare the capacity of newly developed epidermal growth factor receptor(EGFR)-targeted immune magnetic liposomes(EILs) vs epithelial cell adhesion molecule(Ep CAM) immunomagnetic beads to capture colorectal circulating tumor cells(CTCs).METHODS EILs were prepared using a two-step method, and the magnetic and surface characteristics were confirmed. The efficiency of capturing colorectal CTCs as well as the specificity were compared between EILs and Ep CAM magnetic beads. RESULTS The obtained EILs had a lipid nanoparticle structure similar to cell membrane. Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. The binding increased as the contact time extended. Compared with Ep CAM immunomagnetic beads, EILs captured more CTCs in peripheral blood from colorectal cancer patients. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues. CONCLUSION EGFR antibody-coated magnetic liposomes show high efficiency and specificity in capturing colorectal CTCs.展开更多
Various biotin-modified liposomes incorporated with docetaxel(DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modifi...Various biotin-modified liposomes incorporated with docetaxel(DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome(PDL), 0.5%(mol) biotin modified liposome(0.5 BDL), 1%(mol) biotin modified liposome(1 BDL) and 2%(mol) biotin modified liposome(2 BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency(EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5 BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5 BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.展开更多
INTRODUCTIONSite-specific delivery of therapeutic drags to their targetcells is a major scientific challenge for the pharmaceuticalsciences.It offers a number of advantages overconventional drag administration.With dr...INTRODUCTIONSite-specific delivery of therapeutic drags to their targetcells is a major scientific challenge for the pharmaceuticalsciences.It offers a number of advantages overconventional drag administration.With drag targeting,high local concentrations of the drag can be achieved,thuscircumventing many unwanted side effects.Various展开更多
Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomeno...Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside(APM) lipid derivative DSPE-PEG 2000-APM(DPM), and 4-aminophenyl-β-L-fucopyranoside(APF) lipid derivative DSPE-PEG 2000-APF(DPF) were conjugated and modified on alendronate sodium(AD) liposomes to specifically target and deplete KCs. The dualligand modified PEGylated liposomes(MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes(PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What’s more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon.展开更多
Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-...Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.展开更多
Objective:To verify the trypanocidal effectiveness of aescin and aescin liposomes against Trypanosoma evansi in vitro and in vivo.Methods:Aescin and aescin liposomes were used in vitro on trypomastigotes at different ...Objective:To verify the trypanocidal effectiveness of aescin and aescin liposomes against Trypanosoma evansi in vitro and in vivo.Methods:Aescin and aescin liposomes were used in vitro on trypomastigotes at different concentrations(0.5%,1.0%and 2.0%) and exposure times(0,1,3,6 and 9 h).In vivo tests were performed using mice as the experimental model.Trypanosome evansi infected mice were treated with aescin and aescin liposomes with doses of 60 and 100 mg/kg during 4 d.Results:The three concentrations tested in free form and nanoencapsulated showed trypanocidal activity in vitro,completely eliminating the parasites in small concentration after6 h of assay.Animals treated with aescin(100 mg/kg) and aescin liposomes(100 mg/kg)showed increase in longevity,however without curative effect.Conclusions:Active compounds present in natural products,such as aescin,may potentiate the treatment of trypanosomosis when used in association with other trypanocidal drugs.展开更多
Liposomes are phospholipid bilayer vesicles,which are biocompatible,biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications.In this review,we discuss the prospect of using liposom...Liposomes are phospholipid bilayer vesicles,which are biocompatible,biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications.In this review,we discuss the prospect of using liposome technology in the development of a vaccine for tuberculosis.Tuberculosis remains an important health problem that requires the development of an effective vaccine,especially since the only approved vaccine for it continues to be the Bacille Calmette-Geurin(BCG)one developed 100 years ago.This review focuses on the different applications of liposomes toward achieving this goal.Numerous liposomal formulations showing prospect in the research stage and in clinical trials are discussed.展开更多
Tributyrin,a triglyceride analog of short chain fatty acid butyrate,can act as a prodrug of an anticancer agent butyrate.In view of other reports that demonstrated the improved characteristics of conventional liposome...Tributyrin,a triglyceride analog of short chain fatty acid butyrate,can act as a prodrug of an anticancer agent butyrate.In view of other reports that demonstrated the improved characteristics of conventional liposomes by incorporating small amount of nonphospholipids such as Tween 80,herein we sought to investigate whether the incorporation of tributyrin into the liposomal layers may provide additional advantages for liposomes as an anticancer drug carrier.Liposomes were prepared with dimyristoylphosphatidylcholine as a main phospholipid with or without addition of tributyrin.Celecoxib was loaded in liposomes as a model anticancer drug.Tween 80-incorporated liposomes were also prepared for comparison.Tributyrin-incorporated liposomes were ineffective in enhancing the skin permeation of celecoxib compared to Tween 80-incorporated ones.However,tributyrin-incorporated liposomes enhanced the entrapped celecoxib concentration to an extent comparable to Tween 80-incorporated ones.Furthermore,tributyrin-incorporated liposomes exhibited much higher stability compared to Tween 80-incorporated ones.Finally,the cellular uptake of celecoxib loaded in tributyrin-incorporated liposomes into mouse melanoma cells were more than 10-fold higher compared to that loaded in conventional-and Tween 80-incorporated liposomes.Taken together,the incorporation of tributyrin into conventional liposomes loaded with anticancer drugs may provide an advanced anticancer drug carrier delivering both drug and tributyrin.展开更多
The purpose of this study was to develop liposomal formulations of Asparagus racemosus root extract(AR1-6)as well as evaluate the physicochemical properties and in vitro tyrosinase inhibitory activity.Liposomes compos...The purpose of this study was to develop liposomal formulations of Asparagus racemosus root extract(AR1-6)as well as evaluate the physicochemical properties and in vitro tyrosinase inhibitory activity.Liposomes composed of AR1-6 to lipid weight ratio of 1:10 and lecithin(LEC)or Phospholipon90G(PC90G)as structural phospholipid at 7:3 molar ratio to CHOL were prepared by various methods,i.e.chloroform-film(CF),reverse-phase evaporation(REV),polyol dilution(PD),and freeze-drying of monophase solution(MFD)methods.The results revealed that vesicles prepared by CF and MFD were multilamellar whereas those prepared by REV and PD were oligolamellar in nature with particle sizes ranging from 0.26 to 13.83 mm.The zeta potentials were in the range of1.5 to39.3 mV.AR1-6 liposomes with LEC possessed significantly higher entrapment than those with PC90G.The highest entrapment efficiency and in vitro tyrosinase inhibitory activity of 69.08%and 25%,respectively,were obtained from liposomes having LEC and prepared by PD method.The tyrosinase inhibitory activity were in the rank order of LEC>PC90G,and PD>CF>REV>MFD.It could be concluded that the mechanism of vesicle forming in each method of preparation was the key factor influencing physicochemical properties,particularly vesicle type,size,surface charge,and entrapment,which were well correlated with the biological activity.展开更多
The liposome is the first nanomedicine transformed into the market and applied to human patients.Since then,such phospholipid bilayer vesicles have undergone technological advancements in delivering small molecular-we...The liposome is the first nanomedicine transformed into the market and applied to human patients.Since then,such phospholipid bilayer vesicles have undergone technological advancements in delivering small molecular-weight compounds and biological drugs.Numerous investigations about liposome uses were conducted in different treatment fields,including anti-tumor,anti-fungal,anti-bacterial,and clinical analgesia,owing to liposome's ability to reduce drug cytotoxicity and improve the therapeutic efficacy and combinatorial delivery.In particular,two liposomal vaccines were approved in 2021 to combat COVID-19.Herein,the clinically used liposomes are reviewed by introducing various liposomal preparations in detail that are currently proceeding in the clinic or on the market.Finally,we discuss the challenges of developing liposomes and cutting-edge liposomal delivery for biological drugs and combination therapy.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.
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.
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National Natural Science Foundation of China (No.31671020) for financial support
文摘Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.
基金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.
文摘pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.
文摘Liposomes have been widely researched as a delivery system and there have been many manufacturing techniques used in the production of liposomal preparations,the most common being extrusion method which will be introduced in this paper.However because of the unique properties of liposomes and their susceptibility to chemical and physical degradation,sterilisation remains an unresolved issue in the manufacturing of liposomebased formulations.It is especially pertinent in the pharmaceutical industry where liposomes are commonly prepared for intravenous administration.Currently,filtration and aseptic manufacturing are recommended for the preparation of sterile liposomal products.Newer aseptic manufacturing techniques such as dense gas techniques have been devised to eliminate the need for terminal sterilisation.This paper will highlight the limitations of the conventional techniques that are specific to the liposome preparation under the respective sterilisation conditions specified by the 2011 British Pharmacopoeia to achieve 106 Sterility Assurance Level,as well as modifications incorporated in the newer sterilisation technologies to overcome these limitations.This paper will introduce these techniques in brief,including their advantages and limitations.
文摘AIM To compare the capacity of newly developed epidermal growth factor receptor(EGFR)-targeted immune magnetic liposomes(EILs) vs epithelial cell adhesion molecule(Ep CAM) immunomagnetic beads to capture colorectal circulating tumor cells(CTCs).METHODS EILs were prepared using a two-step method, and the magnetic and surface characteristics were confirmed. The efficiency of capturing colorectal CTCs as well as the specificity were compared between EILs and Ep CAM magnetic beads. RESULTS The obtained EILs had a lipid nanoparticle structure similar to cell membrane. Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. The binding increased as the contact time extended. Compared with Ep CAM immunomagnetic beads, EILs captured more CTCs in peripheral blood from colorectal cancer patients. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues. CONCLUSION EGFR antibody-coated magnetic liposomes show high efficiency and specificity in capturing colorectal CTCs.
文摘Various biotin-modified liposomes incorporated with docetaxel(DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome(PDL), 0.5%(mol) biotin modified liposome(0.5 BDL), 1%(mol) biotin modified liposome(1 BDL) and 2%(mol) biotin modified liposome(2 BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency(EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5 BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5 BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.
基金Science Fundation of Science and Technology Committee of Guangdong Province,№97031
文摘INTRODUCTIONSite-specific delivery of therapeutic drags to their targetcells is a major scientific challenge for the pharmaceuticalsciences.It offers a number of advantages overconventional drag administration.With drag targeting,high local concentrations of the drag can be achieved,thuscircumventing many unwanted side effects.Various
基金supported by the National Natural Science Foundation of China (Nos. 81373334 and 81573375)
文摘Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside(APM) lipid derivative DSPE-PEG 2000-APM(DPM), and 4-aminophenyl-β-L-fucopyranoside(APF) lipid derivative DSPE-PEG 2000-APF(DPF) were conjugated and modified on alendronate sodium(AD) liposomes to specifically target and deplete KCs. The dualligand modified PEGylated liposomes(MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes(PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What’s more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon.
基金financially supported by National Basic Research Program of China(973 Program,2015CB931802)Natural Science Foundation of China(31470968 and 81627901)。
文摘Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.
基金Support by Fundacao de Amparo a Pesquisa do Rio Grandedo Sul(FAPERGS),Grant No.002071-2551/13-6
文摘Objective:To verify the trypanocidal effectiveness of aescin and aescin liposomes against Trypanosoma evansi in vitro and in vivo.Methods:Aescin and aescin liposomes were used in vitro on trypomastigotes at different concentrations(0.5%,1.0%and 2.0%) and exposure times(0,1,3,6 and 9 h).In vivo tests were performed using mice as the experimental model.Trypanosome evansi infected mice were treated with aescin and aescin liposomes with doses of 60 and 100 mg/kg during 4 d.Results:The three concentrations tested in free form and nanoencapsulated showed trypanocidal activity in vitro,completely eliminating the parasites in small concentration after6 h of assay.Animals treated with aescin(100 mg/kg) and aescin liposomes(100 mg/kg)showed increase in longevity,however without curative effect.Conclusions:Active compounds present in natural products,such as aescin,may potentiate the treatment of trypanosomosis when used in association with other trypanocidal drugs.
基金supported by Fundamental Research Grant Scheme (FRGS/1/2018/SKK08/USM/03/1),Ministry of Higher Education (Malaysia)Long-term Research Grant Scheme (LRGS/1/2015/USM/01/1/1),Ministry of Higher Education (Malaysia)
文摘Liposomes are phospholipid bilayer vesicles,which are biocompatible,biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications.In this review,we discuss the prospect of using liposome technology in the development of a vaccine for tuberculosis.Tuberculosis remains an important health problem that requires the development of an effective vaccine,especially since the only approved vaccine for it continues to be the Bacille Calmette-Geurin(BCG)one developed 100 years ago.This review focuses on the different applications of liposomes toward achieving this goal.Numerous liposomal formulations showing prospect in the research stage and in clinical trials are discussed.
基金This work was partially supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(2012R1A1A2042768)by Grant No.A092018 of the Korean Health Technology R&D Project funded by the Ministry for Health,Welfare&Family Affairs,Republic of Korea.
文摘Tributyrin,a triglyceride analog of short chain fatty acid butyrate,can act as a prodrug of an anticancer agent butyrate.In view of other reports that demonstrated the improved characteristics of conventional liposomes by incorporating small amount of nonphospholipids such as Tween 80,herein we sought to investigate whether the incorporation of tributyrin into the liposomal layers may provide additional advantages for liposomes as an anticancer drug carrier.Liposomes were prepared with dimyristoylphosphatidylcholine as a main phospholipid with or without addition of tributyrin.Celecoxib was loaded in liposomes as a model anticancer drug.Tween 80-incorporated liposomes were also prepared for comparison.Tributyrin-incorporated liposomes were ineffective in enhancing the skin permeation of celecoxib compared to Tween 80-incorporated ones.However,tributyrin-incorporated liposomes enhanced the entrapped celecoxib concentration to an extent comparable to Tween 80-incorporated ones.Furthermore,tributyrin-incorporated liposomes exhibited much higher stability compared to Tween 80-incorporated ones.Finally,the cellular uptake of celecoxib loaded in tributyrin-incorporated liposomes into mouse melanoma cells were more than 10-fold higher compared to that loaded in conventional-and Tween 80-incorporated liposomes.Taken together,the incorporation of tributyrin into conventional liposomes loaded with anticancer drugs may provide an advanced anticancer drug carrier delivering both drug and tributyrin.
基金The financial support from the Thai Herbal NanoCosmeceuticals Coordinated Research Program,National Nanotechnology Center,National Science and Technology Development Agency,Thailand is gratefully acknowledged.
文摘The purpose of this study was to develop liposomal formulations of Asparagus racemosus root extract(AR1-6)as well as evaluate the physicochemical properties and in vitro tyrosinase inhibitory activity.Liposomes composed of AR1-6 to lipid weight ratio of 1:10 and lecithin(LEC)or Phospholipon90G(PC90G)as structural phospholipid at 7:3 molar ratio to CHOL were prepared by various methods,i.e.chloroform-film(CF),reverse-phase evaporation(REV),polyol dilution(PD),and freeze-drying of monophase solution(MFD)methods.The results revealed that vesicles prepared by CF and MFD were multilamellar whereas those prepared by REV and PD were oligolamellar in nature with particle sizes ranging from 0.26 to 13.83 mm.The zeta potentials were in the range of1.5 to39.3 mV.AR1-6 liposomes with LEC possessed significantly higher entrapment than those with PC90G.The highest entrapment efficiency and in vitro tyrosinase inhibitory activity of 69.08%and 25%,respectively,were obtained from liposomes having LEC and prepared by PD method.The tyrosinase inhibitory activity were in the rank order of LEC>PC90G,and PD>CF>REV>MFD.It could be concluded that the mechanism of vesicle forming in each method of preparation was the key factor influencing physicochemical properties,particularly vesicle type,size,surface charge,and entrapment,which were well correlated with the biological activity.
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 82073782)the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(zdsys-202103)。
文摘The liposome is the first nanomedicine transformed into the market and applied to human patients.Since then,such phospholipid bilayer vesicles have undergone technological advancements in delivering small molecular-weight compounds and biological drugs.Numerous investigations about liposome uses were conducted in different treatment fields,including anti-tumor,anti-fungal,anti-bacterial,and clinical analgesia,owing to liposome's ability to reduce drug cytotoxicity and improve the therapeutic efficacy and combinatorial delivery.In particular,two liposomal vaccines were approved in 2021 to combat COVID-19.Herein,the clinically used liposomes are reviewed by introducing various liposomal preparations in detail that are currently proceeding in the clinic or on the market.Finally,we discuss the challenges of developing liposomes and cutting-edge liposomal delivery for biological drugs and combination therapy.
