Ethosomal Gel Research Articles

Transdermal ethosomal gel nanocarriers; a promising strategy for enhancement of anti-hypertensive effect of carvedilol

The current study was conducted to develop vesicular ethosomal gel (ethogel) systems for upgrading the transdermal delivery of anti-hypertensive carvedilol. Ethosomes composed of Phospholipon 100 H, cholesterol, ethanol, and Transcutol P at different ratios, were prepared by thin-film hydration method with sonication. Carvedilol-loaded ethosomes were characterized by microscopic examinations followed by other in-vitro assessments. Selected ethosomal formulation (E10) was incorporated into different concentrations of gelling agents to prepare the ethogel formulations. Ethogels were subjected to physicochemical characterization, compatibility, and in-vitro drug release studies. Ex-vivo skin permeation and retention studies were performed followed by in-vivo studies in induced hypertensive rats. The smooth ethosomes demonstrated vesicular size of 201.55–398.55 nm, entrapment efficiency of 30.00–90.66% and loading capacity of 7.64–43.04% with zeta potential range of −30.30 to −44.90 mV. The homogeneous ethogels exhibited appropriate results of pH and drug content measurements. Spreadability was observed as a function of viscosity as the latter increased, the former decreased. The ethogel formulation (G2) manifested satisfactory physical appearance, spreadability, viscosity, and in-vitro release. In comparison to pure carvedilol gel, tested formulations (E10 and G2) developed high ex-vivo permeation, steady-state flux and drug retention through skin layers. The in-vivo study of G2 formulation revealed a significant gradual decline (p < 0.01) in the mean arterial pressure of rats at the second hour of experiment (146.11 mmHg) with continuous significant decrease (p < 0.001) after 6 h (98.88 mmHg). In conclusion, ethogels as promising lipid carriers proved their potential to enhance skin permeation with extended anti-hypertensive action of carvedilol.

In-vivo Evaluation of the Wound Healing Activity of the Sesamum Indicum L. Seed Extract in Novel Ethosomal Vesicular System

Aim: To establish the wound healing activity of Sesamum indicum L. of seed extract in novel ethosomal vesicles. Methods: The ethosomal vesicles were formulated with prepared seed extract of Sesamum indicum L. by solvent evaporation method and characterized it. The optimized ethosomal vesicles then incorporated into gel base for further in vivo study in wistar rat. The evaluation of the wound healing activity was performed by using two models i.e. incision and excision models. In excision model percentage wound contraction and period of epithelialization were established for both the extracts. In incision model the parameter which was carried out was breaking strength of wounded skin. Results: The results revealed that the percentage wound contraction, period of epithelialization in excision model was enhanced than that of other groups and tensile strength of skin in incision model was similar to that of standard treated group.&#x0D; Keywords: Sesamum indicum L., Wound Healing, Ethosomal gel.

Pharmacokinetic and pharmacodynamic studies of etodolac loaded vesicular gels on rats by transdermal delivery.

BackgroundThe present study includes the development of liposomal and ethosomal gels for transdermal delivery to overcome the side effects associated with oral route.MethodsThe liposomes and ethosomes were prepared by 32 factorial design using film hydration and cold methods, respectively. Different concentrations of liposomal (ETO-LG) and ethosomal (ETO-EG) gels were prepared at 1%, 2 and 3% (w/v) using carbopol 940 NF. 1%w/v ETO-LG & ETO-EG were optimized upon rheological studies of prepared gels. The optimized gels were further characterized for various physicochemical properties and biophysical studies using FTIR, pharmacokinetic (PK) and pharmacodynamic (PD) studies. The pharmacodynamic activity was performed using carrageenan paw oedema model. The prepared vesicular gels were compared with 45% v/v ethanolic ETO-solution and marketed gel PROXYM® in all the characteristic parameters.ResultsThe pharmacokinetic study reveals that the half life of etodolac in ETO-EG was 1.56 folds whereas ETO-LG showed 1.31 folds higher than PROXYM®. The mean residence time (MRT) of etodolac in ETO-EG and ETO-LG is increased in 1.57 and 1.25 folds, respectively, when compared to PROXYM®. The ETO-EG showed higher percentage reduction in oedema (81.67%) compared to other test products.ConclusionThe pharmacokinetic and pharmacodynamic studies indicated that the vesicular gels show better results compared to PROXYM®. The correlation coefficient value between PK and PD was found to be 0.9635. Graphical abstract ᅟ

Glibenclamide loaded Ethosomal Gel for Transdermal Delivery: Formulation, optimization and ex - vivo study

Glibenclamide loaded Ethosomal Gel for Transdermal Delivery: Formulation, optimization and ex - vivo study

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis.

Dual-release mechanism of ethosomal gels (ie, ethosomes and gel) makes them as versatile drug delivery systems for topical applications. Clove oil is obtained from the clove buds exhibited broad antifungal and antibacterial activity. Cutaneous candidiasis is the infection caused by Candida albicans or other Candida species. The aim of the present study was to prepare ethosomal gel of clove oil and evaluate its effectiveness in the treatment of cutaneous candidiasis. Ethosomes of clove oil was formulated by using varying concentrations of soyaphosphotidyl choline and ethanol, and later, it was incorporated into carbapol 974 base gels to form ethosomal gel. The prepared ethosomal gels were also evaluated for spreadability, drug release studies, ex vivo permeation study, and antifungal activity. The optimized formulation did not cause any irritation to the skin since the pH of formulation was in the pH range of skin. The ethosomal gel showed satisfactory antifungal activity against the fungus C.albicans compared to pure clove oil. The results showed that developed formulation could be promising one in the topical delivery of clove oil for the treatment of cutaneous candidiasis.

Silver Sulfadiazine Nanoethogel for Burn Healing: Characterization and Investigation of Its In Vivo Effects

Nanoethosomal formulation containing silver sulfadiazine(SSD) was used to reduce bacterial burden and healing time in burn injuries. Ethosomal formulations were characterized for their size, ζ-potential, morphology, drug encapsulation efficiency and in vitro release kinetics of SSD. The optimized nanoethosomal suspension with a size of 206.7±1.18, and ζ-potential value of -67.3±0.45mV exhibited a high SSD encapsulation efficiency (92.03±0.79%). Results of antimicrobial tests indicated SSD-loaded ethosome formulation led to a significant reduction of colony number. Histopathological results demonstrated a wound contraction rate of 96.83% for the group treated with SSD ethosomal gel while untreated group showed 59.41%. The SSD ethogels promotes the therapeutic effect of SSD for burn treatment.

Development, Characterization and Transdermal Delivery of Dapsone and an Antibiotic Entrapped in Ethanolic Liposomal Gel for the Treatment of Lapromatous Leprosy

Background and Objective: Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. The aim of present study was to prepare and characterize ethosomes of antileprotic drug Dapsone (DAP) together with an antibiotic Cloxacillin Sodium (CLXS) which may deliver these drugs to targeted site more efficiently than marketed gel preparation of DAP and also overcome the problems related with oral administration of CLXS. Methodology: Ethosomes were prepared by cold method then characterized for particle size, Entrapment Efficiency (EE), zeta potential and permeation studies. Vesicular size was determined by Scanning Electron Microscopy (SEM) and found to be varied from 127±9.01 to 215±7.23 nm depending on the concentrations of soya lecithin and ethanol. Results: The average percent drug entrapment efficiency of formulations ranged between 52.31% to 73.51% and 49.07% to 71.91% for DAP and CLXS respectively. The high ethanol concentration in ethosomes has shifted the vesicular charge from positive to negative. It was observed that F1 and F2 formulations were having zeta potential of -25.08±1.03 mV and -50.11±1.97 mV respectively and do not aggregate rapidly. The drug release of ethosomes ranged from 84.68% to 96.58% and 64.89% to 84.21% for DAP and CLXS respectively. Ethosomal gel was prepared with optimized ethosome and studied for its release and physicochemical characteristics. Conclusion: Finally, G5 demonstrated better (p &lt; 0.05) antileprotic effect to improve effectiveness, stability and to reduce side effects and toxicity associated with the chosen drugs in order to treat Leprosy.

Formulation Optimization and In-vitro and In-vivo Evaluation of Lornoxicam Ethosomal Gels with Penetration Enhancers.

Ethosomes, a novel type of percutaneous drug delivery carrier with a lipid bilayer structure, penetrate the skin barrier due to their deformability and malleability, and presence of ethanol that fluidizes lipids in the skin. In order to further enhance the delivery of drugs through the skin, penetration enhancers are widely used. The objective of this work was to develop an optimized formulation of lornoxicam ethosomal gels, investigate skin permeability with the addition of penetration enhancers, and evaluate the invivo pharmacodynamics of these formulations. Lornoxicam ethosomes were prepared by the ethanol injection method and optimized using the orthogonal design method. Lornoxicam ethosomal gels with enhancers were prepared and optimized using in-vitro transdermal delivery experiments. Experiments on lornoxicam ethosomal gels containing various enhancers such as azone, menthol, lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion cells to measure the percutaneous permeability of the different formulations. Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal gels were examined using the hot-plate and acetic acid-induced writhing tests. Anti-inflammatory activity was investigated using the dimethylbenzene-induced mouse ear swelling method. The results showed that compared to other formulations, the optimized lornoxicam ethosomal gels with 5 % menthol significantly increased transdermal penetration. Meanwhile, the optimized lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti-inflammatory activity compared with the plain lornoxicam gels. These results suggest that the optimized ethosomal gel formulated in this study is a promising lornoxicam carrier in transdermal delivery systems to enhance anti-nociceptive and antiinflammatory efficiency.

DEVELOPMENT AND OPTIMIZATION OF RIZATRIPTAN BENZOATE ETHOSOMES

Objective: The objective of this study was to assess the development of ethosomal drug delivery system for site-specific topical delivery of rizatriptan benzoate (RBZ) for sustained action.Methods: In the present study ethosomes were prepared using the cold method. The formulation was optimized using 33 full factorial designs. The lipid concentration (X1), ethanol concentration (X2) and stirring speed (X3) were selected as independent factors and the vesicle size (Y1) and % entrapment efficiency (Y2) were selected as dependent variables.Results: The equation of multiple regression revealed that there was no significant interaction among factors. The lipid concentration had a positive effect on vesicle size while ethanol concentration and stirring speed had a negative effect. For entrapment efficiency, all factors showed a positive effect while lipid concentrative found to be the main influencing factor. The formulation F4E459 (4% SPC, 45% v/v ethanol 900 RPM), which was characterized by optimum vesicle size (5.5 µm) and high entrapment efficiency (93.32%), was considered to be an optimal formulation. The scanning electron microscopy (SEM) results showed that RBZ ethosome have a smooth surface. The polydispersity index (PI) and zeta potential of the optimized formulation were found to be 0.493±0.021and–21.3 mV respectively. In vitro permeation through rat abdominal skin from the ethosomal gel followed Higuchi diffusion model over a period of 8 h.Conclusion: The results obtained in this research work clearly indicated a promising potential of ethosomal carrier system of RBZ for migraine treatment with a topical approach for sustained action.

Preparation and Evaluation of Mangifera Indica Loaded Ethosomal Gel for Anti-Inflammatory Activity in Animal Model

Preparation and Evaluation of Mangifera Indica Loaded Ethosomal Gel for Anti-Inflammatory Activity in Animal Model

Development and Antimicrobial Evaluation of Binary Ethosomal Topical Gel of Terbinafine Hydrochloride for the Treatment of Onychomycosis

The objective of this investigation was to prepare and evaluate the binary ethosomal gel containing terbinafine HCl (TH) to treat onychomycosis. It was reported that binary ethosomes possessed good permeation and stability characteristics than ethosomes. Binary ethosomes of TH were prepared by film hydration method. Prepared binary ethosomes were evaluated for optimized system. Further, ex-vivo skin permeation studies were conducted with rat skin. The formulation of binary ethosomes was converted to gel by using carbopol 934 and evaluated for rheological properties. Antifungal testing of gel was done by cup plate method, using Candida albicans and zones of inhibition of growth were measured. The size, ZP and EE of the prepared binary ethosomes ranged from 200-320nm, -20 to -30mV and 70-92% respectively. In-vitro and ex-vivo diffusion studies indicated that formulation BE4 with greater amount of binary alcoholic phase, showed faster release and increased flux over others. SEM studies revealed that binary ethosomes were in spherical shape. Based on size, EE, drug release profile and antifungal studies, the BE4 formulation was selected for gel preparation. The prepared 0.5% binary ethosomal BE4 gel showed good content uniformity, pH 5.5, no skin irritation, good consistency and better rheological behaviour. Further, antifungal studies of BE4 gel indicated that gel had lower antifungal activity than plain BE4 formulation, probably due to gelling effect in agar diffusion studies. In conclusion, we developed a pharmaceutical gel containing binary ethosomes of BE4 having TH to provide anti-fungal effects useful for the treatment of onychomycosis. &#x0D;

Formulation, Development and Evaluation of Nano Ethosomal Gel of Tramadol Hydrochloride

Formulation, Development and Evaluation of Nano Ethosomal Gel of Tramadol Hydrochloride

Formulation and in vitro stability evaluation of ethosomal carbomer hydrogel for transdermal vaccine delivery

The primary objective of this study was to develop, evaluate and compare the effectiveness and stability of ethosomal carbomer gels in different solvents. The optimal ethosomal formulation was isolated to create ethosomal gels using carbomer in either pure water (water gel) or PBS containing 30% ethanol (PBS gel). In vitro release of the ethosomal gels were tested using Franz apparatus on hydrophilic and hydrophobic artificial membranes. In vitro stability of two ethosomal gels was systematically evaluated. Transdermal antigen delivery of ethosomal gel was finally performed on the skin of hair removal mice. Both solvent and concentration effects on the in vitro release performance of ethosomal gel of carbomer have been confirmed. Penetration depth has been found to be dependent on the nature of the membranes such that penetration rate is higher in the hydrophobic membrane than the hydrophilic ones. Furthermore, in vitro stability test indicated that ethosomal PBS gel was more stable than ethosomal water gel. In vivo immunoassay confirmed that the ethosomal PBS gel could deliver the antigenic molecules into the skin of mice and stimulate specific IgG secretion. Using the same solvent for lipid vesicular formulation when making polymeric hydrogel may help to provide a more conducive environment for lipid vesicles and hence enhance their roles in transdermal antigen delivery.

A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: in-vitro and in-vivo characterization.

BackgroundBetahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects.ObjectiveThe aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control.Materials and methodsBox–Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux. The morphology and zeta potential of the optimized formulation were evaluated. The % drug release, flux, and pharmacodynamics of the optimized formulation gel were studied.ResultsThe size and entrapment efficiency percent had a direct positive relationship with the concentration of PC and negative relationship with ethanol and PG. The % drug release and flux decreased with increasing PC and PG, while ethanol enhanced both responses. Regression modeling indicated a good correlation between dependent and independent variables, where F16 was chosen as the optimized formulation. F16 showed well-defined spherical vesicles and zeta potential of −24 mV, and % release from the gel exceeded 99.5% over 16 h with the flux of 0.28 mg/cm2/h. Food intake and weight gain of rats were significantly decreased after transdermal application of the BDH ethosomal gel when compared with control, placebo, and BDH gel. The histopathological findings proved the absence of inflammation and decrease in adipose tissue.ConclusionResults obtained showed a significant, sustained transdermal absorption of BDH ethosomal gel and, consequently, a decrease in food intake and weight gain.

PENETRATION TEST OF CAFFEINE IN ETHOSOME AND DESMOSOME GEL USING AN IN VITRO METHOD

Objectives: Caffeine has many functions including its use in the field of cosmetics. Nonetheless, the percutaneous absorption of caffeine is very low(9%), and the penetration of a substance such as caffeine in the skin is not desirable. Ethosomes and desmosomes are lipid vesicles created by themodification of liposomes containing phospholipids and ethanol or dimethyl sulfoxide (DMSO) as the penetration enhancer. The purpose of this studywas to compare the effectiveness of ethosomes and desmosomes as vesicles in increasing the penetration of caffeine.Methods: Ethosomes and desmosomes were prepared using phosphatidylcholine, ethanol/DMSO, and caffeine. Phosphatidylcholine was used in theform of phospholipon 90 g that was obtained from soybeans. Observations were done including the characteristic of ethosomes and desmosomes,organoleptic observation, homogeneity observation, and in vitro penetration test using Franz diffusion cell method.Results: The cumulative penetration of caffeine ethosome gel is 3316.46±218.51 μg/cm2, with flux 249.45±30.06 μg·cm−2·hr−1, and 62.35±4.52%. Thecumulative penetration of the desmosome gel is 2954.95±222.87 μg/cm2 with flux 381.68±34.91 μg·cm−2·hr−1 and 53.4±3.65%.Conclusions: It can be concluded that ethosome is more effective than desmosome in increasing the penetration of caffeine.

HAIR GROWTH ACTIVITY AND SAFETY TEST OF ETHOSOMAL GEL ETHYL ACETATE FRACTION OF NOTHOPANAX LEAVES (NOTHOPANAX SCUTELLARIUM MERR.)

Objective: The aims of this study were to know the hair growth activity from the ethosomal gel of ethyl acetate fraction compared to the nonethosomal gel of ethyl acetate fraction, as well as its ability to penetrate into the skin and its safety from ethosomal gel testing.Methods: The hair growth activity was measured by three parameters: Hair length, hair thickness, and hair weight.Results: The results obtained are shown that the ethosomal gel with concentration 1% has better hair growth activity rather than the ethosomal gel with concentration 0.5% and the nonethosomal gel but it has similarity to the positive control (minoxidil gel with concentration 2%). In vitro penetration test using Franz diffusion cells shown that the ethosomal gel with concentration 1% has cumulative penetration of quercetin higher than nonethosomal gel, which value was 3.3175±0.02 μgcm−2 for the ethosomal gel with concentration 1%; and 2.7663±0.19 μgcm-2 for the nonethosomal gel with flux values for the ethosomal gel with concentration 1% and the nonethosomal gel, respectively, are 0.4147±0.01 μgcm−2h−1 and 0.3458±0.02 μgcm−2h−1.Conclusion: As for the safety test using hen’s egg test-chorioallantoic membrane (HET- CAM) safety test) have shown that both concentrations 0.5% and 1% of the ethosomal gel can generate mild irritation for topical application.

Novel Transdermal Ethosomal Gel Containing Green Tea (Camellia sinensis L. Kuntze) Leaves Extract: Formulation and In vitro Penetration Study

Background: One of the natural products that have many benefits is green tea ( Camellia sinensis L.). It can be used to maintain health because of its high antioxidant activity from epigallocatechin gallate (EGCG). However, EGCG has a low ability to penetrate through the skin due to its hydrophilicity. The aim of this study is to improve the penetration of EGCG through the skin by lipid nanovesicle, namely ethosome. Methods: Ethosomes were made using thin layer hydration method. Ethosomes were formulated with different concentration, equal to 1% (F1), 1.5% (F2), and 2% (F3) of EGCG from green tea leaves extract. They were characterized, then a chosen formula would be formulated into a gel dosage form (ethosomal gel). A gel without ethosome (non-ethosomal gel) was prepared as a control. Both of them were evaluated their penetration enhancement ability using Franz diffusion cells with the abdomen skin of Sprague-Dawley rats. Results and Discussion: Based on the results, F1 had a spherical shape, Dv90 129.00 ± 0.00 nm, polydispersity index 0.05 ± 0.00, zeta potential at -62.6 ± 5.05 mV, and the highest entrapment efficiency of 54.39 ± 0.03 %. The cumulative amount of EGCG penetrated from ethosomal and non-ethosmal gel were 1364.28 ± 56.32 μg/cm 2 and 490.17 ± 2.60 μ g/cm 2 , respectively ( p μ g/cm 2 . hour and 31.09 ± 0.29 μ g/cm 2 . hour, respectively. Conclusion: It can be concluded that ethosomal gel can increase the penetration of EGCG from green tea leaves extract. Key words: EGCG, Epigallocatechin Gallate, Ethosomes, Franz Diffusion Cell, Green Tea Leaves Extract, in-vitro Penetration Test.

A SIMPLE (HPLC–UV) METHOD FOR THE QUANTIFICATION OF COLCHICINE IN BULK AND ETHOSOMAL GEL NANO-FORMULATION AND ITS VALIDATION

Objective: To develop and validate a stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method for the determination of colchicine in bulk and ethosomal gel nano-formulation.Methods: The chromatographic conditions were optimized using stainless steel Hypersil Gold C-18 analytical column with the dimensions of 250 mm x 4.6 mm ID x 5 µm. The mobile phase consisted of acetonitrile and ammonium acetate buffer (20 mmol/l, pH=4.85) in the ratio of 32:68 v/v. The flow rate was set at 1 ml/min and the detection wavelength was 353 nm. The column was maintained at 30 °C and the injection volume was 10 µl. The stability of colchicine in different conditions was investigated by exposing the drug to stress degradation using acid, base, oxidation, heat and light.Results: There was no interference from excipients, impurities, dissolution media or degradation products at the retention time of colchicine 5.9 min indicating the specificity of the method. The limit of detection (LOD) and the limit of quantification (LOQ) were 8.64 ng/ml and 26.17 ng/ml respectively. The drug showed good stability under heat, acid, oxidation and light, but substantial degradation was observed under alkali condition. The procedure was validated for specificity, linearity, accuracy and precision.Conclusion: A simple, rapid, specific and stability-indicating HPLC–UV method for the determination of colchicine in the pure and ethosomal gel was successfully developed. The developed method was statistically confirmed to be accurate, precise, and reproducible.

Formulation of Mefenamic Acid Loaded Ethosomal Gel by Hot and Cold Methods

Formulation of Mefenamic Acid Loaded Ethosomal Gel by Hot and Cold Methods

In vitro Penetration and Bioavailability of Novel Transdermal Quercetin-loaded Ethosomal Gel

Quercetin has been widely used to treat many diseases because of its high antioxidant activity. However, it has low oral bioavailability and penetration through the skin. The aim of this research was to enhance penetration and bioavailability of quercetin using transdermal ethosomal gel. Three ethosomal formulae, E1 (1%), E2 (1.5%) and E3 (2%) with different concentration of quercetin were prepared using thin-film hydration method. Their physical properties were characterized, and then a selected ethosomal formula was incorporated into a gel dosage form. Two gels, one ethosomal and the other non-ethosomal were prepared. In vitro penetration using Franz diffusion cells and bioavailability study in Sprague Dawley male rats were carried out. Results showed that E2 was the chosen formula to be incorporated into the gel dosage form. According to the in vitro penetration study, the diffusion flux of quercetin from the ethosomal and non-ethosomal gels were 343.35±17.69 ng/cm2/h and 120.68±11.92 ng/cm2/h, respectively (P<0.05). In the bioavailability study, ethosomal gel showed higher maximum concentration (Cmax) and area under curve (AUC0-t) when compared to non-ethosomal gel and oral suspension. Cmax from the ethosomal gel, non-ethosomal gel, and oral suspension were 413.49±28.64 ng/ml, 189.46±49.68 ng/ml, and 61.92±14.31 ng/ml, respectively (P<0.05). AUC0-t from the ethosomal gel, non-ethosomal gel, and oral suspension were 4035.15±560.60, 584.87±265.46, and 431.21±239.85, respectively (P<0.05). In conclusion, ethosomal gel could increase penetration and bioavailability of quercetin compared to non-ethosomal gel.