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Objective To study the antitumor effect of natural active compound usenamine (C18H17NO6, 6-acety1-2- (1-amino-ethylidene)-7,9-dihydroxy-8,9b-dimethy1-9bH-dibenzofuran-1,3-dione) nano-liposomes in vitro and in vivo. Methods Nano-liposomes were prepared by thin film dispersion-ultrasonic method. The drug loading of nano-liposomes was determined by HPLC. The cancer cells were cultured in vitro, and the absorbance values were measured by MTT method to evaluate the anticancer effect in vitro. A nude mouse xenograft model was established to observe the growth inhibitory effect of drug-loaded nano-liposomes on tumor growth in nude mice. Results The drug loading of drug-loaded nano-liposomes was 1.26 mg/mL. The IC50 of the drug-loaded nano-liposomes in the XWLC-05, HCT-116, and HepG2 cells were 2.48 μg/mL, 0.86 μg/mL, and 1.86 μg/mL, respectively, and the inhibition rates of XWLC-05, HCT-116, and HepG2 cells administered at a dose of 4 μg/mL were 85.59%, 99.95%, and 96.91%, respectively (P < 0.01). The minimum relative tumor proliferation rate of nude mice was 50.98%, and usenamine nano-liposomes had antitumor effect in vivo. Conclusion The natural active compound usenamine can be prepared as a nano-liposome.In vitro cell experiments showed that usenamine nano-liposomes had a dose-effect relationship with cancer cells. In vivo experiments in nude mice found that drug-loaded nano-liposomes had inhibitory effect on tumors.
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Objective To investigate the therapeutic effect and mechanism of non-mitogenic acid fibroblast growth factor 1( NMFGF1) on diabetic cardiomyopathy ( DCM) by using PEG-modified nano-liposomes combined with ultrasound-targeted microbubble destruction technique ( UTMD ) . Methods The NMFGF1 loaded PEG-modified nano-liposomes were prepared by a water-in-water emulsion method and their quality inspections were also investigated. Type 1 diabetes animal model was induced by intraperitoneal injection of streptozotocin ( 70 mg/kg) in male SD rats. The diabetic rats were raised twelve weeks after the diabetes model was established and DCM rats were selected by ultrasonic heart function examination. After two weeks of intervention, all rats were kept for another two weeks and then underwent transthoracic echocardiography examination. The rats were sacrificed and myocardial tissue was obtained to quantify myocardial collagen fraction ( CVF ) and cardiac myocyte apoptotic index by Sirius red staining and TUNEL staining. Results NMFGF1-loaded PEG-nano-liposomes showed a good morphology and 90.3％± 1.4％ NMFGF1 encapsulation efficiency. Compared with DCM group, NMFGF1group, and NMFGF1-PEG-nano-liposomes group, NMFGF1-loaded PEG-nano-liposome plus UTMD group showed increased left ventricular end diastolic diameter (LVIDd) [(7.36±0.42) vs (5.75±0.24), (6.64±0.27), (6.72±0.24)mm, all P<0.05]and leftventricularfractionshortening(LVFS) [(50±3) vs (33±2), (44±5), (43±3)mm, all P<0.05], and decreased left ventricular posterior wall thickness (LVPW) [(1.65±0.07) vs (1.89±0.08), (1.73±0.11), (1.73 ±0.07) mm, all P<0.05], with decreased CVF and apoptotic index(all P<0.05). Conclusion PEG-nano-liposomes combining with UTMD technique has a greater translational potential in the delivery of NMFGF1 for the treatment of DCM by attenuating oxidative stress-induced injury and may provide a promising strategy for treating diabetes cardiomyopathy.
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OBJECTIVE： To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes， and to optimize its preparation technology. METHODS： The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size， encapsulation efficiency and drug-loading amount as indexes， the weight ratio of phospholipid to drug （mg/mg）， the weight ratio of phospholipid to cholesterol （mg/mg） and ultrasonic time （min） as factors， central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS： The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL（r＝0.999 7）； precision， stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1（mg/mg）； the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 （mg/mg）； the ultrasonic time was 10 min. Under this technology， the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were （200.5±25.1） nm and （11.02±0.20）％， relative errors of which to predicted value （196.3 nm， 10.68％） were 1.82％ and 1.63％. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS： Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.
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ABSTRACT Orthosiphon aristatus (Blume) Miq., Lamiaceae, is a medicinal plant from Southeast Asia. Pharmacological effects of O. aristatus are attributed to the presence of lipophilic flavones. This study aimed to carry out accelerated stability studies on O. aristatus ethanolic extract and its nano liposomes. The extracts were exposed to four different temperatures at 30, 40, 50 and 60 °C for 6 months. The samples were analyzed at 0, 1, 2, 3, 4, 5 and 6 months by high performance liquid chromatography using rosmarinic acid, 3′-hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin and eupatorin as markers. Different chemical kinetic parameters of the markers were evaluated by Arrhenius equation to predict shelf life (t90) at different storage conditions and at room temperature. Moreover, the stability of O. aristatus ethanolic extract and O. aristatus nano liposomes were analyzes by chemical fingerprinting using FTIR spectroscopy, principal component analysis and hierarchical clustering analysis. The degradation of markers in both O. aristatus ethanolic extract and O. aristatus nano liposomes followed the first order degradation reaction (dependening on their initial concentration). The loss of marker compounds in O. aristatus ethanolic extract, stored at 30, 40, 50 and 60 °C for six months were up to 25, 52, 72 and 89% for all compounds, respectively. However, in O. aristatus nano liposomes 16, 71, 85 and 100% of compounds were lost during 6 months of storage at 30, 40, 50 and 60 °C, respectively. Therefore, the markers in O. aristatus nano liposomes seems to be more stable at a temperature below 30 °C compared to O. aristatus ethanolic extract. However, markers present in O. aristatus ethanolic extract are more stable at a higher temperature (above 30 °C). principal component analysis or hierarchical clustering analysis analyses were applied to the FTIR results in order to demonstrate the discrimination between extracts based on the storage conditions. The results show that the functional group of the components in the extracts and their chemistry relationship is influenced by the temperature setup indicating the extracts are not stable during the storage conditions.
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Objective To investigate the prevention effect of curcumin loaded nano - liposomes on diabetic cardiomyopathy. Methods The curcumin-loaded nano-liposomes were prepared by Film dispersion and ultrasonic hydration technology and their quality inspections were also investigated.Sixty SD rats were randomly divided into normal control group,model control group,blank and curcumin-loaded nano-liposomes group ( n＝15). Diabetes model was induced by intraperitoneal single injection of STZ(70 mg·kg-1).After two weeks of STZ injection,the rats with model control were used for this study.The curcumin loaded nano-liposomes treatment group rats were treated with curcumin loaded nano-liposomes ( 5 mg·kg-1) via caudal vein administration for 12 weeks (three times a week).Rats of normal control group,blank nano-liposomes treated group and model control group were administrated equivalent volume of 0. 9% sodium chloride solution or blank nano-liposomes solution. After treatment for 12 weeks,the experimental animals underwent ultrasonic heart function examination.Then the rats were sacrificed and their hearts were arrested after saline perfusion. The myocardial cell collagen volume fraction ( CVF) and apoptosis index were detected. Results Curcumin loaded nano-liposomes showed good morphology and curcumin encapsulation efficiency ( 88. 37 ± 1.21) %with high stability and dispersibility. From the animal experiments, the evaluation indexes in curcumin loaded nano-liposomes treated group including LVIDd and LVFS were significantly higher than model control group and nano-liposomes treated group(P<0.05),and the LVPW,CVF and apoptosis index were significantly lower than model control group and nano-liposomes treated group(P<0.05). Conclusion Curcumin loaded nano-liposomes can improve the cardiac function of diabetic rats by reducing the fibrosis and apoptosis index of myocardial cells in diabetic rats, which could be used to prevent the diabetic cardiomyopathy.
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Objective To investigate the advanced preventive effect of acid fibroblast growth factor (aFGF) on diabetic cardiomyopathy(DCM) by using heparin-modified nano-liposomes combined with ultrasoundtargeted microbubble destruction technique (UTMD).Methods aFGF-loaded nano-liposomes (aFGF-lips) were prepared by lyophilization technique.Type Ⅰ diabetes model was induced by intraperitoneal injection of streptozotocin (STZ,70 mg/kg) in male SD rats.Before and twelve weeks after intervention,all rats underwent the transthoracic echocardiography.The segmental mean peak systolic radial velocity (Vs),systolic circumferential strain (Sc),and systolic circumferential strain rate (SRc) were measured.The expression of aFGF in DCM rats was detected by western blot.The rats were sacrificed and myocardial tissue were stained with masson staining and Tunel staining to quantify myocardial collagen fraction(CVF) and cardiac myocyte apoptosis index(AI).Results aFGF-lips showed good morphology and aFGF encapsulation efficiency (89.4±1.2)％ with high stability.From the animal experiments,the echocardiographic indexes including Vs,Sc and SRc had significantly improvements over DM group (P＜0.05) and all other treatment group (P＜0.05).The Masson's trichrome staining demonstrated that CVF was significantly higher in DM group than in the control group and was significantly lower in the aFGF-loaded nano-liposome+UTMD group than other groups(all P＜0.05).The TUNEL results showed that AI was significantly higher in DM group than in the control group and was significantly lower in aFGF-loaded nano-liposome +UTMD group than other groups (all P＜0.05).Conclusion aFGF nano-liposome combining with UTMD technique can improve the functions and pathologies of the hearts in type 1 diabetes mellitus model,which might provide a novel technique for aFGF in DCM prevention.
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Objective To prepare palmatine-loaded flexible nano-liposomes (PFL) films with Bletilla striata polysaccharide (BSP) as membrane material, and evaluate its pharmacy related performance in order to lay the foundation for further application. Methods The PFL was prepared by injection method and the films of PFL based on Bletilla striata polysaccharide (PFL-BPF) was prepared by homogenate coating method. The PFL-BPF was characterized and evaluated by electron microscopy, differential scanning calorimeter (DSC), and in vitro transmucosal membrane experiment. Results The PFL and BSP had good compatibility and easy to film with BSP as membrane material. The appearance of PFL-BPF obtained was smooth, non-bubble, flexible, and suitable stiffness; PFL-BPF had good biological adhesion. The time of scouring the film agent from mucous membrane with normal saline was (130 ± 7) min. At 0.5 h, the dose of PFL-BPF promoting palmatine (PA) infiltration to mucosa was 32.41 μg/g. It was 3.17 times higher than those of PA solution based on BSP (PL-BPF) and 1.9 times for PA common liposomes based on BSP (BLP + PA-BPF) (t-test, P < 0.05); At 2.5 h, it was 2.67 times and 1.89 times higher than those of PL-BPF and BLP + PA-BPF, respectively. It showed that PFL-BPF could significantly promote the water-soluble drug PA through mucosa membrane and release it slowly. The results of DSC showed that the possible mechanism for promoting the absorption of PA through mucosa membrane was that the flexible liposomes disturbed the mucosal epithelial cells and carried the drug into the mucosal tissue. Conclusion The PFL-BPF had the advantages of good film-forming property, lasting adhesive attraction, strong scour resistance, simple and feasible preparation process, and could promote drug permeation into mucosa obviously. Therefore, the flexible nano-liposomes film is a good drug carrier for the transmucosal drug delivery applications and has a wide application prospect.
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Objective: To optimize the preparation method of triptolide-nano-liposomes (TP-NLS). Methods High pressure homogeneous method was used to prepare TP-SLN. According to even design U7(73), the preparation method of TP-SLN was optimized with the factors including weight ratio of phosphorlipid and cholesterol (A), quantity of Poloxamer 188 (B), and homogeneous pressure (C), using the encapsulation efficiency (EE), particle size, and Zeta potential of NLS as indexes. Results: The optimum prescription of TP-NLS was A1B5C7, i.g. lipid matrix a : b was 6 : 1, the dosage of Poloxamer 188 was 1.3 g, and the homogeneous pressure was 70 MPa, high pressure homogeneous method for 15 min. The TP-NLS prepared with the optimal method had good appearance. The EE was 83.52%, the average particle size was 117 nm, and the Zeta potential was 31.7 mV. TP-NLS solution was kept in avoiding light environment at 4℃ for 30 d, and the preservation stability was good. Conclusion: The formula is reasonable and the preparation method of TP-NLS is feasible, which is valuable to further study.
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Objective: To explore the optimum preparation process of triptolide nanometer coating agent. Methods: Optimum preparation process was investigated by uniform design with the amount of film forming material such as polyethylene glycol 124 (PVA124), carbomer, CMC-Na, and the mixing time as investigating factors, and with uniformity, film-forming ability, and peeling strength as indexes. We conducted sc simulation experiment in vitro to investigate the percutaneous penetration process of triptolide nanometer coating agent. Results: The best way to prepare triptolide nanometer coating agent is that we use glycerol monostearate 1.6 g, glycerin 0.25 g, PVA124 3.9 g, Carbomer 0.6 g, CMC-Na 0.9 g, and mix them in 150 min. With above preparation process, we can achieve better coating agent. JS was 0.350 µg/(cm2·h) and the cumulative permeation quantity in 24 h was 11.534 µg/cm2. Conclusion: Using the optimum preparation process, we can get better triptolide nanometer coating agent, which is uniform, easy coating,good adhesion with skin, strong flexibility, and drying soon.
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At present, there is no specific antidote for local anesthetic toxicity, which seriously hindered therapeutic efficts of clinical treatment. It is increasingly urgent for finding find the effective antidote to local anesthetic. This article at-tempts to interpret the molecular pharmacological mechanism from fat pool, energy metabolism, NO, ion channel and solubili-zation for the role of fatty acids in reversal of myocardial toxicity of local anesthetics. And the different characteristics of the structure and function of nano liposome and fat emulsion were compared.
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AIM: To compare brucine with the mixed solution of brucine and nano-liposomes to observe analgesic and anti-inflammatory effects of the brucine nano-liposome for local use on skin were studied. METHODS: The effects of brucine,brucine and nano-liposomes mixed solution,brucine nano-liposome,on the edema of mouse ear induced by dimethylbenzene and the writhing induced by acetic acid were investigated. RESULTS: The results showed that brucine nano-liposomes exhibited better anti-inflammatory and analgesic activities than the brucine.(P