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Objective: The resveratrol nanocarrier complex (Res-PAMAM-Ac) was encapsulated by polyamide-amine dendrimer, its stability and safety was investigated. Methods: The blank carriers were synthesized by the divergence method and acetylated. Characterization of the nanocarriers was investigated by 1H-NMR and IR. The properties of carriers were investigated by particle size and zeta potential. Res-PAMAM-Ac was prepared by reverse-phase evaporation method, and the drug loading, encapsulation rate and stability were examined by HPLC. The cytotoxicity of nanocarriers and complex on human lung cancer A549 cells were investigated by MTT method. The biosafety of nanocarriers and complex was inspected by hemolysis test. Results: Res-PAMAM-Ac nanocarrier complex was synthesized successfully. The particle size of Res-PAMAM-Ac was (167.30 ± 21.70) nm, PDI was 0.115 ± 0.006 and the zeta potential was (19.27 ± 0.35) mV. The average drug loading of Res-PAMAM-Ac was (76.99 ± 1.30) mg/g and the encapsulation rate was (29.63 ± 2.7)%. The stability parameter (KE) was less than 0.15, no obvious drug precipitation was observed. Cytotoxicity tests showed that Res-PAMAM-Ac was less toxic to human lung cancer A549 cells when the concentration was below 30 μg/mL. The hemolysis rate of the nanocarriers and complex was less than 5%, which can be considered as biosafety. Conclusion: Res-PAMAM-Ac nanocarrier complex with uniform particle size, high stability, good drug loading and low toxicity was prepared.
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OBJECTIVE： To optimize the preparation technology of Celastrol nanostructured lipid carriers （Cel-NLC）， and to characterize it. METHODS： Cel-NLC was prepared by melt-emulsification ultrasonic method. Based on single factor test， using encapsulation rate of Cel as index， the ratio of liquid lipid （the ratio of total mass）， the amount of compound emulsifier and the dose of main drug were optimized by central composite design-response surface methodology. Validation test was conducted. Zeta potential and particle size of Cel-NLC that prepared by optimal prescription were determined by using granularity and Zeta potential analyzer. The morphology of liposome was observed by TEM. RESULTS： The optimal prescription included that the ratio of liquid lipid was 39％；the amount of compound emulsifier was 196 mg；the dose of main drug was 8 mg. The average encapsulation efficiency of 3 batches of Cel-NLC was 87.22％； average particle size was （41.2±1.1） nm，and average Zeta potential was （－18.4±0.2） mV （n＝3）. It was spherical under electron microscopy. CONCLUSIONS： The optimized technology is simple， stable and feasible， and it is suitable for the preparation of Cel-NLC.
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Objective To prepare the puerarin-loaded PEGylated mesoporous silica nanoparticles (PUE@PEG-MSNs) and evaluate its protection on the acute myocardial ischemic rats. Methods PEG-MSNs functionalized mesoporous silica nanoparticles were achieved by the condensation method, and then they were loaded by PUE. The morphology of PUE@PEG-MSNs was examined by detection methods of particle diameter, Zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectra (FTIR). Moreover, the drug loading and encapsulation rate were measured by HPLC. Sixty acute ischemic myocardial model rats were prepared by coronary artery ligation, and then they were randomly divided into six groups: Sham, MIRI model, puerarin injection, low-, mid-, and high-dose PUE@PEG-MSNs groups. Different doses of PUE@PEG-MSNs and puerarin injection were given 5 min after the ligation. Monitoring the changes of ST, the blood was collected at the end of reperfusion for detecting the changes of serum creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and malondialdehyde (MDA). The myocardial infarct size was also determined. Results PUE@PEG-MSNs presented uniform spherical morphology and particle size distribution. The particle size and Zeta potential was 300 nm and -30 mV respectively. The drug loading and entrapment efficiency was 14.7% and 67.8% respectively. Both puerarin injection and PUE@PEG-MSNs could reduce the ST-elevation of electrocardiogram, decrease the contents of CK, LDH, AST, and MDA, and reduce the myocardial infarct size. The efficacy of mid- and high-dose PUE@PEG- MSNs groups was better than that of puerarin injection group. Conclusion PUE@PEG-MSNs were successfully prepared and exerted the protective effects on the acute myocardial ischemic rats.
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Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome (Lac-CTD- lips) and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow: cantharidin: hydrogenated soya lecithin:cholesterol at 1:20:5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 mL of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was (123.9 ± 4.8) nm (n = 3), the particle size distribution was single-peak, the zeta potential was (-0.36 ± 0.81) mV (n = 3), and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.
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OBJECTIVE:To prepare borneol-modified colchicine ethosome,and to evaluate its in vitro transdermal permeation. METHODS:Borneol-modified colchicine ethosome was prepared with ultrasonic injection-probe ultrasonic method,and its ethosome was characterized. The content and moditication rate of borneol in borneol-modified colchicine ethosome was determined by GC;content and encapsulation rate of colchicine was determined by HPLC.Accumulative permeability and permeation rate were investigated for colchicine ethanol solution,colchicine-borneol-ethanol solution,colchicine ethosome without borneol-modification, borneol- modified colchicine ethosome after diffused for 1,3,6,8,12,16,24,48 h. RESULTS:The average particle size of borneol- medified colchicine ethosome was about(110.4 ± 5.1)nm,polydispersity index was 0.110 ± 0.030,Zeta potential was (2.33±0.20)mV,prepared ethosome is approximately spherical in shape and multilaminar vesicles in structure. Encapsulation rate of colchicine was 56.12%,and modification rate was 9.85%. The in vitro diffusion tests showed that after diffused for 48 h, accumulative permeability per unit area of borneol-modified colchicine ethosome was 103.52 μ g/cm2;permeation rate was 1.26 times as colchicine ethosome without borneol-modification,1.77 times as colchicine-borneol-ethanol solution and 5.14 times as colchicine ethanol solution. CONCLUSIONS:Prepared borneol-modified colchicine ethosome has small particle size,narrow particle size distribution,high modification rate and good transdermal permeation.
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Objective To optimize the preparation process of honokiol long-circulating liposomes (HLCL) and study the in vitro and in vivo release. Methods An orthogonal experiment was designed to optimize the composition of HLCL using entrapment efficiency as evaluation indicator. The liposome surface morphology was observed by transmission electron microscope (TEM), and the liposome release in vitro was studied by dialysis method. The concentration of honokiol in rat plasma was determined by the established LC-MS/MS method, and the differences in pharmacokinetic parameters were compared after honokiol and HLCL (20 mg/kg) were orally administered to SD male rats, respectively. Results The optimal composition of HLCL was 8:1:1 for soya phosphatidyl choline-cholesterol-mPEG2000-DSPE, and 1:10 for honokiol-liposome materials with the ultrasonic time of 12 min. Under the optimized conditions, HLCL was sphere with mean particle size of 121.5 nm and mean Zeta potential of -30.8 mV, the encapsulation efficiency and drug-loading content was 84.7% and 10.4%, respectively. In vitro release results showed that the liposomes could be gently and slowly release with the 24 h cumulative release rate at pH 1.2 and pH 6.9 dissolve medium of 80% and 71%, respectively. Based on the pharmacokinetic results, Cmax, tmax, and t1/2 were (23.29 ± 11.76) ng/mL, (0.13 ± 0.05) h and (10.59 ± 5.72) h for HLCL, and (79.34 ± 56.32) ng/mL, (0.30 ± 0.07) h and (4.44 ± 3.14) h for honokiol, respectively. There was no significant difference about the AUC0-∞ following oral administration of honokiol and HLCL at isodose honokiol (20 mg/kg). Conclusion Compared with honokiol, HLCL was released gently and slowly in vitro, absorpted rapidly and eliminated slowly in vivo.
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Objective To optimize the formulation of sinomenine hydrochloride transfersomes (SHTs) and to verify their therapeutic effects on rheumatoid arthritis in rats. Methods SHTs were prepared by ethanol injection method. Their formulation was optimized by an orthogonal test, which was based on the elasticity of transfersomes. Elasticity of transfersomes was measured by constant pressure extrusion method and entrapment efficiency was measured by HPLC combined with centrifugation ultrafiltration. The model of rheumatoid arthritis was established by subcutaneous injection of type II collagen into Wistar rats' tail. The therapeutic effects of the preparation on rheumatoid arthritis in rats were evaluated based on ankle joint score, swelling degree, level of TNF-α and IL-1β in serum as well as histological changes including inflammatory cell infiltration, pannus formation, cartilage destruction, and bone erosion. Results The optimized formulation was as follows: egg phospholipid 300 mg, cholesterol 30 mg, sinomenine hydrochloride 100 mg, sodium deoxycholate 60 mg, vitamin E 5 mg, phosphate buffered saline (pH 8.0) 23 mL, and absolute ethyl alcohol 2 mL. The optimized transfersomes had an average size of (83.31 ± 0.08) nm, Zeta potential of (-32.57 ± 3.27) mV, deformability index of 38.69 ± 1.66, drug content of (2.96 ± 0.27) mg/mL, and entrapment efficiency of (39.82 ± 0.97) %. The results of pharmacodynamical test revealed that the preparation could significantly reduce joint swelling caused by rheumatoid arthritis (P < 0.01) and lower TNF-α and IL-1β level in serum (P < 0.01), effectively alleviate inflammatory response and improve histological changes of ankle joint. Conclusion The preparation process for the transfersomes is feasible and their quality can be controlled. The optimized SHTs are effective for treatment of rheumatoid arthritis in rats.
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Aim: To prepare the influenza vaccine lyophilized liposomes and to characterize its particle distribution, encapsulation efficiency and immunogenicity. Methods: Flu vaccine liposome based on the method of thin-film evaporation was prepared using phospholipids , cholesterol and the purified influenza virus split vaccine, and was further subjected to frozen-drying. The polymorph was observed by microscope; the particle distribution and the average size were analysed by transmission electron microscope; its encapsulation efficiency was determined by Lowry method and the antibody titers were assessed by hemagglutination-inhibition after pulmonary delivery to mice. Results: The reconstitated influenza vaccine liposome under electronic microscope were round or elliptic particles evenly distributed at a mean size of 2. 14 祄, with the encapsulation efficiency of more than 80%. The antibody titer through pulmonary delivery was higher than that through intraperitoneal injection. Conclusion: The prepared influenza vaccine lyophilized liposomes possess high encapsulation efficiency, better particle distribution and marked immunogenicity through pulmonary delivery to mice. Pulmonary delivery of influenza vaccine liposomes is a potential immunization approach worthy of further exploitation.
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Objective:To perform in vitra MR imaging and compare the differences between DepoGd and Gd-DTPA in signal intensity using multivesicular liposome(DepoFoam)as the carrier of rutine magnetic resornance contrast media.Methods:Lipos ome such as cholesterol was mixed with Gd-DTPA,and rotation speed of centrifuge was adjusted to get DepoGd particles with certain diameter.The three different liquors named X,Y and Z(Gd-DTPA liquor,17 ?m DepoGd liquor and 22 ?m DepoGd liquor) were prepared into 4 kinds of concentrations spectively.Signal intensity of these liquors was measured with MR scanner,and statistical analysis was done consequently.Results:Diameters of most of the DepoGd particles got through the forementioned method with the envelop rate of 50%.Signal intensity of different liquors with the same concentration showed no statistical difference,which means signal intensity of DepoGd and Gd-DTPA active compound with the same mole concentration showed no statistical difference in vitra MR test.Conclusion:DepoFoam can carry conventional MR contrast agent with high envelop rate and no obvious difference was showed in signal intensity.
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Objective The microcapsules were prepared by using chitosan and sodium alginate as wall materials,and the controlled-release microcapsulas of interferon tau were hoped to be develop an oral interferon preparation.Methods The microcapsules were prepared by using syringe hand-made drop.In the process of dropping,speed and distance were the major factors which influence the form of microcapsules.Results Chitosanalginate microcapsules which was prepared simple and fast had high encapsulation rate and extended-release effect in intestine.Conclusion Chitosan-alginate microcapsules have the potential to be used to prepare interferon tau and other protein medicines.