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Objective: To compare the effects of softeners including ethanol, propylene glycol and mixed alcohol (ethanol-propylene glycol 2:8) on the preparation of glabridin ethosomes (GLA-ES), and provide the selection basis of the softeners for studying the ethosomes of insoluble drugs. Methods: GLA-ES were prepared by injection-ultrasonic binding method with ethanol, propylene glycol and mixed alcohol (ethanol-propylene glycol, 2:8) as softeners. The morphology, size, Zeta potential, entrapment efficiency, stability, and in vitro drug release of GLA-ES were investigated. Tyrosinase activity on melanoma B16-OVA cells were detected to evaluate the inhibition of GLA-ES on the synthesis of melanin, the experiment of potassium ferricyanide reducing power was performed to evaluate the antioxidant effect of GLA-ES, and human epidermal HaCaT cells and rat skin were used for preliminary safety evaluation. Results: GLA-ES were yellow translucent liquid, containing vesicular phospholipid bilayer structure, the average particle size of GLA-Et-ES, GLA-PG-ES and GLA-MA-ES were (34.24 ± 0.29), (62.31 ± 1.66) and (41.20 ± 1.13) nm, respectively; The Zeta potential were (-41.0 ± 1.8), (-32.9 ± 0.2) and (-35.8 ± 1.6) mV, the entrapment efficiency were (91.47 ± 2.39)%, (87.33 ± 1.31)% and (91.39 ± 3.59)%, respectively, which had good stability of storage at 4 ℃ for 20 d, in vitro drug release behaviors of GLA-ES fitted Higuchi equation, implying their sustained release properties. Compared with the glabridin suspension, the inhibitory effects of GLA-Et-ES, GLA-PG-ES and GLA-MA-ES on tyrosinase activity in melanoma B16-OVA cells were increased by 38.07%, 19.58% and 40.42%, respectively. The results of potassium ferricyanide reducing power also showed that GLA-ES had a stronger in vitro antioxidant effect than the glabridin suspension; GLA-ES were nearly nontoxic on normal cells and had no irritation to rat skin. Conclusion: GLA-ES can be obtained by hree kinds of softeners, which can inhibit the synthesis of melanin and enhance the antioxidant effect with good safety. The present research will provide the basis for further developing skin-whitening cosmetics or pharmaceutical external preparation. For the insoluble drugs such as glabridin, when mixed alcohol (ethanol-propylene glycol) was selected as the softener to prepare ethosome, it exhibited better encapsulation efficiency and stability than that of ethanol or propylene glycol as the softener alone.
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OBJECTIVE: To investigate the release characteristics in vitro of chitosan coated curcumin ethosomes (CMETS-CS) and its pharmacokinetics in rats. METHODS: The in vitro cumulative release rate of CMETS-CS in two different media (pH 1.2 HCl and pH 6.8 PBS solution) was investigated by dynamic dialysis. The release behavior was evaluated by similar factor method. After gastrointestinal administration, the plasma drug concentration at different time point was determined by high performance liquid chromatography (HPLC), and the average plasma concentration-time curve was drawn. The pharmacokinetic parameters, bioequivalence between CMETS-CS and CM were analyzed by DAS software. RESULTS: The cumulative release rates of CMETS-CS in pH 1.2 HCl and pH 6.8 PBS solution were (70.49±0.75)%, (73.90±0.52)%, respectively. Compared with CM, the CMETS-CS significantly increase the drug release.The release behavior of CMETS-CS in the two different release media was similar. After calculation, the area under the 0-72 h curve (AUC0-72 h), mean residence time (MRT0-72 h), peak concentration (ρmax) of CMETS-CS were 11.84, 5.45, 1.55 times than those of free curcumin (CM), respectively and its relative bioavailability of CMETS-CS was 1 111.32%. The bioequivalence of AUC0-72 hAUC0-∞ and tmax and in CMETS-CS and CM were not eligible, but bioequivalence of ρmax was eligible. CONCLUSION: Compared with free curcumin, CMETS-CS can improve the release behavior in vitro, significantly improve the oral bioavailability in rats, and there is not bioequivalence between CMETS-CS and CM.
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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 establish an HPLC method for determination of matrine in matrine ethosome thermosensitive gels. Methods Matrine was detected in matrine ethosome thermosensitive gels by using a YMC-Pack NH2 column(4.6 mm× 150 mm,5 μm),with the mobile phase containing acetonitrile-ethanol(9: 1).The flow rate was 0.8 mL·min-1 ,the column temperature( 25 ± 2) ℃ and the UV detection wavelength 215 nm. Results The peak area correlated with matrine concentration within the range of 1.00-100.00 μg·mL-1 linearly,and the average correlation coefficient was 0.999 2.The average recoveries rate of low,medium and high concentration of matrine were 98.16%,98.15%,98.00%,respectively,and the RSD were 0.30%,0. 69%,0. 71%,respectively. Conclusion The method is simple,sensitive and accurate. With the advantages of specificity,high precision,good stability and repeatability,the HPLC method can be used for the determination of matrine in matrine ethosome thermosensitive gels.
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OBJECTIVE:To prepare nicotine ethosome and study its transdermal permeability in vitro. METHODS:Injection method was adopted to prepare nicotine ethosome. Single-factor test was conducted to study the effects of the amounts of ethanol and phospholipid on the particle size and encapsulation efficiency of the ethosome. Franz diffusion cell was employed to conduct permeability test on excised rat skin to compare cumulative permeating quantities of the nicotine in nicotine ethosome,nicotine lipo-some and nicotine ethanol solution. Confocal laser scanning electron microscope was applied to observe the penetration depths of rhodamine B-containing nicotine ethosome,nicotine liposome and the solution of nicotine ethanol solution in the in vitro rat skin. RESULTS:When the formulation contained 3%(m/V)phospholipid and 35%(V/V)ethanol,the obtained nicotine ethosome had the smallest particle size [(105 ± 11.5) nm] and the highest encapsulation efficiency [(89.13 ± 6.12)%]. Compared with nicotine ethosome and the nicotine ethanol solution,nicotine ethosome had the largest cumulative permeating quantity in vitro at 12 h. Fur-thermore,the above-mentioned 3 preparations all became saturated in permeability at 12 h with the penetration depths of 80 μm, 156 μm and 175 μm,respectively. CONCLUSIONS:The nicotine ethosome that can increase the transdermal permeability of nico-tine has been prepared successfully.
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OBJECTIVE:To compare in vivo and in vitro permeation behaviors of the ethosome gels of testosterone,testoster-one propionate and testosterone undecanoate. METHODS:The ethosome gels of testosterone,testosterone propionate and testoster-one undecanoate were prepared. With cumulative permeating amount and permeation rate as the indexes,Franz diffusion cell and HPLC were employed to compare in vitro permeation behaviors of 3 kinds of ethosome gels in mouse skin. With testosterone patch as the positive control drug, electrochemistry method was adopted to detect the concentration of testosterone in plasma 0,3,6, 9,12,24,36 and 48 h after applying such 3 kinds of ethosome gels on the back of rats,and then pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS:24 h cumulative permeating amounts of the ethosome gels of testosterone,tes-tosterone propionate and testosterone undecanoate were(234.31±13.8),(175.63±41.1)and(72.60±15.3)μg/cm2,and the per-meation rates were(10.25±1.9),(7.64±1.4)and(2.96±0.8)μg/(cm2·h),respectively. The pharmacokinetic parameters of the above-mentioned three kinds of ethosome gels and the positive control drug were respectively as follows as cmax of(20.19±2.57), (17.50±2.91),(0.23±0.04),(14.97±2.12)ng/ml,t1/2Ka of(2.80±0.45),(3.36±0.59),(4.02±0.62),(4.20±0.71)h,AUC0-48 h of(13.85±1.96),(13.93±2.13),(0.35±0.07),(11.76±2.31)ng·h/ml. CONCLUSIONS:in vivo and in vitro permeation behav-iors of the ethosome gels of testosterone and testosterone propionate are fairly good.
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Objective: To study the optimal preparation process of nasal ethosome sprays of volatile oil in Magnoliae Flos after removing a-terpineol alcohol (VOMF) and to investigate its characteristics and mucociliotoxicity. Methods: The 5% VOMF ethosome was prepared with ultrasonic injection method, and the orthogonal test was used to design the formulations of VOMF ethosome which was evaluated by entrapment efficiency and drug loading as indexes. Quality evaluation included appearance, particle diameter distribution, Zeta potential, entrapment efficiency (EE), and stability. The persistent vibration duration (PVD) and percentage of persistent vibration (PPV) in situ toad oral palate cilia were observed to evaluate the mucociliotoxicity administered by various constituents. Results: The optimal preparation was 1.5% of phospholipid, 0.15% of cholesterol, and 36% of ethyl alcohol. The quality evaluation showed that the ethosome was round and uniform, while the mean Zeta potential was (-55.9 ± 2.1) mV. The average particle diameter was getting smaller, the EE had no change, and no mucociliotoxicity was found after spraying. Conclusion: Ultrasonic injection method used to prepare VOMF ethosome is rational and stable and it can be used for nasal administration.
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Transdermal drug delivery system was first introduced more than 30 years ago. The technology generated tremendous excitement and interest amongst major pharmaceutical companies in the 1980s and 90s. By the mid to late 1990s, the trend of transdermal drug delivery system merged into larger organizations. Ethosomes are the ethanolic phospholipid vesicles which are used mainly for transdermal delivery of drugs. Ethosomes have higher penetration rate through the skin as compared to liposomes hence these can be used widely in place of liposomes. Ethosomes have become an area of research interest, because of its enhanced skin permeation, improved drug delivery, increased drug entrapment efficiency etc. The purpose of writing this review on ethosomes drug delivery was to compile the focus on the various aspects of ethosomes including their mechanism of penetration, preparation, advantages, composition, characterization, application and marketed product of ethosomes. Characterizations of ethosomes include Particle size, Zeta potential, Differential Scanning Calorimertry, Entrapment efficiency, Surface tension activity measurement, Vesicle stability and Penetration Studies etc.
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Objective: To optimize the preparation technology of geniposide ethosome spray (GES) and to evaluate the regulation of its nasal mucosa permeability in vitro and nasal ciliotoxicity. Methods: Geniposide ethosomes were prepared by ethanol injection method. An central composite design-response surface method was used to optimize the related factors and technical parameters in the preparation of geniposide ethosomes with entrapment efficiency as evaluation index. Their physical properties were evaluated by the transmission electron microscope and photon correlation spectrometer. The isolated pig nasal mucosa was used to investigate the regulation of GES nasal mucosa permeability in vitro. The accumulated permeation amounts of geniposide aqueous solution, geniposide liposomes, and geniposide ethosomes were compared. In situ toad palate model was established to evaluate the effects of geniposide ethosomes on persistent vibration duration of toad palate cilia, so as to evaluate the cililary toxicity. Results: The average encapsulation percentage, particle size, drug loading, and Zeta potential of geniposide ethosomes were (65.80 ± 2.53)%, (173.40 ± 71.02) nm, (5.25 ± 0.15)%, and (-42.50 ± 8.27) mV, respectively. The accumulative permeation amount of geniposide ethosomes in 300 min was 23.39 μg/cm2, which was about 2.17 times of liposomes and 11.03 times of geniposide aqueous solution. Furthermore, the GES showed less mucociliary toxicity. Conclusion: The optimized formulation and preparation technology of geniposide ethosomes are rational. GES could significantly increase the mucosa permeability of geniposide and could be used for nasal administration.
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Objective: To optimize the two types of colchicine ethosome patches using uniform design and to investigate their in vitro release, transdermal properties, stability, and stimulus. Methods: Two kinds of colchicine ethosomes made of soybean lecithin (SL) and hydrogenated phosphatidy (HP) were prepared using injection method. By the DPS 7.0 sotfware, the uniform design was used to optimize the patch components of colchicines, polyacrylic resin IV, succinic acid, triethyl citrate, and azone in patch pressure-sensitive adhesive, with its initial adhesion and hold tack as indexes. The colchicine ethosomes patches of SL and HP were prepared, respectively. The automated dissolution test analyzer and improved Franz diffusion cell were adopted to compare the in vitro release and transdermal properties of the two types of colchicine ethosomes patches, respectively. Moreover, the preparation stability under different light, humidity, and high temperature conditions was studied, and the skin irritation test for rabbits was carried out. Results: The optimized colchicine ethosome patches by the uniform design adhere with the viscous standards in Chinese Pharmacopeia 2010. The in vitro release of the three types of patches were fitted with the Higuchi equation and their release rates increased in turn, respectively, which were (3.1331 ± 0.3272), (2.8724 ± 0.3481), and (2.3802 ± 0.2134) μg/(cm2·h1/2). Their in vitro transdermal releases were fitted with the zero-class equation and increased in turn, respectively, which were (0.9390 ± 0.0731), (0.8775 ± 0.0908), and (0.6167 ± 0.0816) μg/(cm2·h). During the storage, the HP patches had better stability than the SL patches, especially with the stable color. In the skin irritation test for rabbits, there was no erythema and oedema reactions in 48 h. Conclusion: The HP patches have obviously higer in vitro release rate and transdermal rate, and for its better stability of preparation, the HP patches are superior to the SL ones.
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Objective: To explore the preparation method of glycyrrhetinic acid ethosome (GAE) hydrogel patch and to evaluate its characteristics during in vitro transdermal drug delivery. Methods: GAE was prepared by ethanol infusion method, and its entrapment efficiency, size and surface potential were investigated. Then GAE was used to prepare the hydrogel patch. The amount of penetrated glycyrrhetinic acid was determined by HPLC on modified Franz diffusion cells, and then the in vitro transdermal drug delivery of the prepared hydrogel patch was evaluated. Results: GAE had a spherical or ellipsoidal appearance and a layered structure, with an encapsulation efficiency of (75.63 ± 1. 86)%, a particle size of (106.2 ± 20.54) nm, and a surface potential of (- 41.3 ± 2.8) mV. The percutaneous delivery rate and accumulative infiltration quantity of GAE hydrogel patch were significantly higher than those of glycyrrhetinic acid hydrogel patch. The 24 h accumulative infiltration quantity of GAE hydrogel patch was 5.55 times that of the glycyrrhetinic acid hydrogel patch (t-test, P<0.01). Conclusion: Compared with glycyrrhetinic acid, GAE can significantly improve the in vitro transdermal delivery of hydrogel patch, demonstrating that ethosome hydrogel patch might be an ideal vector for transdermal delivery of glycyrrhetinic acid.