Ethosomal Gel Research Articles

Effect of Physicochemical and Rheological Properties of Ibuprofen Loaded Ethosomal Gel and its Optimization by 32 Factorial Design

The current research work aimed to develop and evaluate the ibuprofen loaded ethosomal gel for transdermal delivery. Ibuprofen is an anti-inflammatory drug. On oral administration, it undergoes extensive hepatic metabolism. It has short biological half-life (1.8-2hr) and low bioavailability (49-70%). To overcome the side effects, it would be preferable to apply via transdermal delivery. Ibuprofen loaded ethosomes were prepared by film hydration technique using 32 factorial design and characterized for various physicochemical parameters. The optimized ethosomes was incorporated into gel using carbopol 940NF as a gel base. The developed gels were tested against rheology, ex vivo skin permeation studies, FTIR studies and stability studies. The prepared ethosomal dispersion shown particle size in the range of 140 nm to 242nm, zeta potential was found in the range of -18 to -36mV, %EE was found in the range of 44 to 84% and in vitro permeation studies were found in the range of 71 to 94% respectively. Based on rheological properties, 1%w/v concentration was optimized among the prepared gels. The ethosomal gel flux was found to be 27µg/cm2/hr which was found as better than other test products. FTIR studies revealed that there was no incompatibity between drug and excipients. Stability studies resulted that the optimum storage condition (2-8°C) doesn’t effect on degradation of physicochemical properties. It was concluded that ethosomes alters physicochemical properties of drug and thus enhances its permeation across the skin. Hence, ethosomes are considered as promising tool for anti-inflammatory therapy via transdermal delivery. Key words: Factorial design, Gel, Rheology, Permeation, Ethosomes

Perspective Impact of Gelling Agents on the Mechanistic Behavior for the Topical Delivery of Flufenamic Acid Nano-Ethosomal Dispersion

Objective: This work involves the preparation and in vitro characterization of a topical gel formulation that is capable of deep skin permeation, providing the anti-inflammatory effect for the optimum nano ethosomal dispersion formula. Methods: The optimum ethosomal dispersion was prepared (in our laboratory) by utilizing 3% flufenamic acid (FA), 30% ethanol, 1% phosphatidylcholine (PC), 10% propylene glycol, and 1% cholesterol by cold method and 20 minutes’ ultra-sonication. Four ethosomal gel formulas (G1-G4) were prepared by using carbopol 934 and carbopol 940 at 1% and 1.5% concentration at a 1:1 ratio as a gelling agent. These formulas were further subjected to in vitro characterization to assess their physical appearance, consistency, viscosity, spreadability, in vitro drug release, and ex-vivo skin permeation and deposition. Results: The results revealed that the formula (G1) demonstrated the best homogeneity, consistency, and spreadability as well as an initial release of 68.53% after 10 hours, that continued up to 89.36% after 24 hours, and a significantly higher drug release percentage at pH 7.4 than pH 5.5 with substantially higher ex vivo abdominal rat skin permeation (60.74%) and deposition percentages (36.87%%) in comparison to flufenamic acid plain gel prepared conventionally which demonstrated 23.73% and 14.96% skin permeation and deposition percentages after 24 hours. Conclusion: This work was successful in preparing a novel topical gel using ethosomal nanocarriers, promoting efficient topical skin delivery of the anti-inflammatory FA with a once-daily application, which improved patient compliance.

Novel Hyaluronic Acid ethosomes based gel formulation for topical use with reduced toxicity, better skin permeation, deposition, and improved pharmacodynamics

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it’s commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of −6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.

Fabrication of Ethosomes Containing Tocopherol Acetate to Enhance Transdermal Permeation: In Vitro and Ex Vivo Characterizations.

Background: Tocopherol acetate (TA) is known as a skin moisturizing and photoprotective agent. One major drawback with tocopherol and its derivatives remains its limited stability. Aim: To develop highly stable TA-containing ethosomal gel (TAEG) as an advanced dosage form. Methods: A cold method technique was used to produce the ethosomes. An in vitro evaluation of viscosity, conductivity, and pH stability was carried out for three months. An in vitro physical characterization of the nanoparticles (NPs) that included particle size (PS), zeta potential (ZP), transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy analysis was then performed. Organoleptic evaluation, thermostability at 8 °C, 25 °C, 40 °C and 40 °C ± 75% RH, pH, conductivity, viscosity, and spreadability measurements were also performed in vitro for three months. An ex vivo permeation study was performed in phosphate-buffered solution (1× PBS; pH 5.5 or pH 7.4) at 37 ± 0.2 °C by using rat abdominal skin and the Franz diffusion cell method. The data of three independent experiments were expressed as mean ± SD. A two-way ANOVA was applied to compare data on TAEG versus TA control gel (TACG). Results: PS of the ethosomes was in the range of 144–289 nm. A total of nine formulations were developed. Optimized TAEG formulation (TA-5) was selected based on the highest entrapment efficiency (EE) of 99.71%, while the stability, the PS, and the uniformity-based polydispersity index (PDI) were also among the best. TA-5 exhibited smooth spherical ethosomal NPs with PS of 200.6 nm, ZP value of −18.6 V, and PDI of 0.465. Stability data obtained for TA-5 in terms of rheology, conductivity, and pH presented no significant change (p > 0.05) during the entire study duration. Rheological studies indicated that TA-5 followed a non-Newtonian behavior of shear thinning system. The ex vivo drug permeation was 44.55 ± 0.01% in TA-5 and the drug retention in skin was 51.20%, which was significantly higher than TACG as observed after 24 h permeation study (p < 0.05). Conclusions: The newly developed TAEG formulation appears promising to enhance the effectivity of TA and its topical application.

Enhanced transdermal delivery of lutein via nanoethosomal gel: Formulation optimization, in-vitro evaluation, and in-vivo assessment

Lutein has low oral bioavailability and penetration through the skin. Therefore, the major objective is the development of ethosomal gel loaded with lutein to enhance dermal deposition of lutein. Lutein-loaded formulation (Lut-eth) was developed and optimized using QbD software. The characterization of Lut-eth formulation was performed using zeta sizing (131.3 ± 1.10 nm) and zeta potential (−21.9 mV) which was later validated by electron microscopy. The lut-eth gel was prepared and values for content uniformity, spreadability, consistency, firmness, and toughness were found to be 97.89 ± 1.05%, 7.29 ± 0.015 gcm/s, 2.495 ± 0.24 g s, 0.210 ± 0.01g, and 0.37 ± 0.01 respectively. Rheological investigation reveals viscosity was 2.56.2 mPa s (millipascal second) and shows high elasticity and stability. whereas, consistency, firmness, toughness, the force of adhesion, and work of adhesion was found to be 2.495 ± 0.24 g s, 0.210 ± 0.01g, 0.37 ± 0.01, −0.23 ± 0.05 N, and −55.61 ± 0.11 N s respectively. The lut-eth gel had a maximum plasma concentration of 9.428 ± 3.5 ng/mL in 4 h with AUC0-1279. 679 ± 9.87 ng h mL−1. The drug release study shows sustain release behavior of prepared formulation and a similar sustain release pattern was observed in and Ex-vivo release studies. Confocal laser microscopy, In-vitro, antioxidant study shows better deposition and improved antioxidant effect of formulation which was further validated by Ex-vivo antioxidant assay. Therefore, bearing in mind all these findings, it can be said that Lut-eth gel could be a novel formulation to improve lutein deposition on skin.

Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice.

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.

Ethosomal gel for rectal transmucosal delivery of domperidone: design of experiment, in vitro, and in vivo evaluation

Despite high efficiency of domperidone (DOM) in prophylaxis of emesis accompanied with radiotherapy and chemotherapy, it still can bother cancer patients by its powerful side effects and difficulty of its oral administration. The study was designed to develop and optimize DOM loaded ethosomal gel for rectal transmucosal delivery. Ethosomal formulations were prepared using a 21, 51 full-factorial design where the impact of lecithin concentration and additives were investigated. The optimum ethosomal vesicles were subsequently incorporated in Carbopol gel base where rheological behavior, spreadability, mucoadhesion, and in vivo pharmacokinetic parameters were studied. Based on Design Expert® software (Stat Ease, Inc., Minneapolis, MN), the optimum formulation illustrated entrapment efficiency of 70.02%±5.52%, and vesicular size of 112 ± 3.3 nm, polydispersity index of 0.32 ± 0.01, zeta potential of −59 ± 0.28 mV, and % drug released after 6 h of 76.30%±2.45%. Moreover, ex vivo permeation through rabbit intestinal mucosa increased four times compared to free DOM suspension. The gel loaded with ethosomes showed excellent mucoadhesion to rectal mucosa. DOM ethosomal gel showed a raise in C max and AUC0–48 of DOM by twofolds compared to free DOM gel. The study suggested that ethosomes incorporated in gels could be an efficient candidate for rectal transmucosal delivery of DOM.

Metformin-loaded ethosomes with promoted anti-proliferative activity in melanoma cell line B16, and wound healing aptitude: Development, characterization and in vivo evaluation

The present work deals with the development of metformin-loaded ethosomes for localized treatment of melanoma and wound healing. Different ethosomal formulations were prepared using different concentrations of ethanol adopting injection technique. The developed formulations were investigated for entrapment efficiency, ex-vivo skin permeation, vesicle size, morphology and permeation kinetics. The optimized formulation was loaded in 5 % carbomer gel that was evaluated for skin permeation, cytotoxic effect against melanoma mice B16 cell line and for wound healing action. Ethosomes having 30 % v/v ethanol displayed superior entrapment for metformin % (55.3 ± 0.07); and a highly efficient permeation via mice skin (85.8 ± 3.7). The related carbomer ethosomal gel exhibited higher skin permeation compared to the untreated metformin gel (P < 0.001). The metformin ethosomes had a substantial antiproliferative activity against melanoma B16 cells compared to corresponding metformin solution as shown by the lower IC50 values (56.45 ± 1.47 and 887.3 ± 23.2, respectively, P < 0.05) and tumour cell viability (P < 0.05). The ethosomal system had a significant wound healing action in mice (80.5 ± 1.9%) that was superior to that of the marketed product Mebo® ointment (56 ± 1 %), P < 0.05.This ethosomal system demonstrated outstanding induction of the mRNA levels of growth factors (IGF-1, FGF-1, PDGF-B and TGF-β) that are essential in the healing process. Those findings were supported by histopathologic examination of wound sections of different treated groups. Thus, the study proved that metformin ethosomes as a promising drug delivery system and a conceivable therapeutic approach for treatment of melanoma and wound healing.

Phytochemical investigations and development of ethosomal gel with Brassica oleraceae L. (Brassicaceae) extract: An innovative nano approach towards cosmetic and pharmaceutical industry

The study was aimed to develop and characterize plant extract (Brassica oleraceae) loaded ethosomal gel for the valuation of cosmeceutical applications with a credence that botanical extracts have a greater capability to be employed in the formulation of advanced pharmaceuticals. Phytochemical profiling via FT-IR analysis, total bioactive contents of different polarity extracts (ethanol, dichloromethane, ethyl-acetate and chloroform) and quantification by using High Performance Liquid Chromatographic (HPLC) assay was carried out. Capabilities against oxidative stress were prodded through 2, 2-Diphenyl-1-picrylhydrazyl (DPPH), reduction potential analyses. Besides this, a correlation amongst total bioactive contents (TPC/TFC) and antioxidant potentials (biological activities) was studied by multi-variate statistical analysis. An augmented ethosomal preparation, after characterization and stability studies was incorporated to the gel matrix of Carbopol-940; Test/ EG (Ethosomal gel) with a Control/NEG (Non-ethosomal gel) formulation. Both formulations were then subjected to in-vitro characterization (organoleptic evaluation, pH, conductivity and rheology) of 90 days. By permeation studies flux (μg/cm2/hr); enhancement ratio was calculated and characterization of release data was done by using different kinetic models. The plant extracts revealed the presence of different functional groups along with 39.6 ± 0.5 mgGAE/g; 26.56 ± 0.4 mgQE/g phenolic and flavonoid contents, respectively; HPLC assay confirmed the existence of Quercetin, Gallic, Caffiec, Benzoic, Syringic and Sinapic Acids with highest antioxidant activity of 87.75% ± 1.18 in hydro-alcoholic fraction. Optimized ethosomal formulation exhibited entrapment efficiency of 68.57 ± 1.25, smallest vesicle size of 228.6 ± 1.17 nm with − 21.3 ± 0.15, zeta potential and a homogeneous size distribution of 0.233 ± 0.02. Significant results were obtained after in-vitro characterization. Both formulations followed Korsmeyer-peppas model with flux 35.499 and 21.731 μg/cm2/hr respectively and enhancement ratio 1.63. Thus, a stable ethosomal loaded gel of Brassica oleraceae extract was successfully developed and characterized for cosmeceutical potential.

Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide.

Herein, we developed an ethosomal hydrogel based on three types of ethosomes: simple, mixed (surfactant-based micelles and lipid vesicles) or binary (comprising two type of alcohols). Ethanol injection was employed for vesicles preparation, and sodium alginate, as gelling agent. We purposed the local-transdermal administration of the off-the-shelf retinoid fenretinide (FENR) for chemoprevention of breast cancer. Rheograms and flow index values for alginate dispersion (without ethosomes) and hydrogels containing simple, mixed or binary ethosomes suggested pseudoplastic behavior. An increase in the apparent viscosity was observed upon ethosome incorporation. The ethosomal hydrogel displayed increased bioadhesion compared to the alginate dispersion, suggesting that the lipid vesicles contribute to the gelling and bioadhesion processes. In the Hen's Egg Test-Chorioallantoic Membrane model, few spots of lysis and hemorrhage were observed for formulations containing simple (score of 2) and mixed vesicles (score 4), but not for the hydrogel based on the binary system, indicating its lower irritation potential. The binary ethosomal hydrogel provided a slower FENR in vitro release and delivered 2.6-fold less drug into viable skin layers compared to the ethosome dispersion, supporting the ability of the gel matrix to slow down drug release. The ethosomal hydrogel decreased by ~ five-fold the IC50 values of FENR in MCF-7 cells. In conclusion, binary ethosomal gels presented technological advantages, provided sustained drug release and skin penetration, and did not precludedrug cytotoxic effects, supporting their potential applicability as topical chemopreventive systems.

Formulation and Evaluation of Ethosomal Gel and Non-ethosomal Gel of S.grandiflora Leaves

The numbers of products based on new drug delivery systems have considerably increased in the past few years, and this growth is projected to carry on in the future. These bio-pharmaceuticals present challenges to drug delivery system because of their different nature and difficulty in delivery through conventional routes. Therefore, further research will focus on the delivery of these complex molecules through different routes, including nasal, pulmonary, vaginal, rectal, etc. The intend of the study was to formulate and evaluate ethosomes of Sesbania grandiflora leaves which may transport the drug to targeted site more efficiently than marketed gel preparation and also overcome the problems related with oral administration of drug. Trans-dermal drug delivery is a technique which can be exploited to overcome the variables, which could affect the oral absorption of drugs such as pH, food intake and gastrointestinal motility. As compared to liposome or hydro-alcoholic solution ethosomal systems were much more capable at delivering a fluorescent probe to the skin in terms of quantity and depth. The formulations were prepared with ethanol, lecithin, propylene glycol, and glycerol and were evaluated. The lecithin (phospholipids) used as a vesicles forming component, polyglycol and ethanol used as a skin penetration enhancer. The drug released of formulated ethosomal gel was 4-5 times improved as compared to non ethosomal gel which directly achieves unparalleled flexibility in formulation. Ethosomal gel successfully addresses the issues relating to the drug delivery of poorly water-soluble drugs, peptides, potent drugs and the release of multi-drugs.

Development of stable tocopherol succinate-loaded ethosomes to enhance transdermal permeation: In vitro and in vivo characterizations.

Tocopherol succinate (TS) represents synthetic derivative of α-tocopherol (vitamin E), it act as anti-aging, moisturizing, and antioxidant. Ultraviolet (UV) photo stability of TS is low, and it cause skin irritation. To develop tocopherol succinate loaded ethosomal gel for topical TS delivery and to evaluate its moisturizing and anti-aging effects. Cold method technique was used to produce ethosomal formulations (N=9) by varying ethanol and lipid concentrations (F1-F9). The most optimized formulation (F5) was selected for further study on the basis of characterization. F5 Formulation was incorporated into gel. Ex vivo permeation study was done by using Franz diffusion cell. Non-invasive in vivo study was performed using corneometer for the evaluation of skin moisture content and skin mechanical properties by using cutometer, for 12weeks on human subjects (N=13). Particle size (PS), zeta potential (ZP) and polydispersity index (PDI), Entrapment efficiency were found to be 179.1nm, -13.7mV and 0.345, and 99.71%, respectively. Transmission electron microscopy (TEM) depicted spherical ethosomal particles. Ethosomal gel and control gel were evaluated for conductivity and pH. Rheological analysis revealed a non-Newtonian flow. The release profile showed initial burst and then, sustained release, release data followed Korsmeyer-Peppas model. TS-loaded ethosomal gel appeared physically stable and showed significant results in terms of skin capacitance and mechanical properties. The prepared ethosomal gel formulation containing TS is more stable with enhanced antioxidant, moisturizing properties, and increased TS deposition into the skin layer.

Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation, in-vitro and ex-vivo evaluation, factorial optimization and clinical assessment in melasma patients

Ascorbic acid (vitamin C) is an antioxidant that is widely used in cosmetics in skincare products. Due to the excessive low stability of ascorbic acid in cosmetic formulations, the stabilized ascorbic acid derivative, magnesium ascorbyl phosphate (MAP) was formulated as vesicular carriers; ethosomes and niosomes. The aim was to deliver MAP at the intended site of action, the skin, for sufficient time with enhanced permeation to get an effective response. Ethosomes were formulated using a full 32 factorial design to study ethanol and phospholipid concentration effect on ethosomes properties. Niosomes were formulated using 23 factorial designs to study the effect of surfactant type, surfactant concentration and cholesterol concentration on niosomes properties. The prepared formulations were evaluated for their Entrapment efficiency, particle size, polydispersity index, zeta potential and % drug permeated. The optimized ethosomal and niosomal formulations were incorporated into carbopol gel and evaluated for their permeation, skin retention and stability. A comparative split-face clinical study was done between the ethosomal and niosomal formulations for melasma treatment using Antera 3 D® camera. The optimized ethosomal and niosomal gels showed comparable controlled permeation and higher skin retention over their ethosomes and niosomes formulations respectively. Magnesium ascorbyl phosphate ethosomal gel showed clinically and statistically significant melanin level decrease after one month while MAP niosomal gel showed clinically and statistically significant melanin level decrease after six months. A combination of MAP ethosomes and niosomes could be promising skincare formulations for melasma and hyperpigmentation short and long-term treatment.

Ethosomal gel: a novel choice for topical delivery of the antipsychotic drug Ziprasidone Hydrochloride

Ethosomal gel: a novel choice for topical delivery of the antipsychotic drug Ziprasidone Hydrochloride

Investigating the potential of Quercetin enthused nano lipoidal system for the management of dermatitis

Objective: The present research work was undertaken to develop quercetin enthused nanolipoidal systems and its characterization. The objective was to investigate potential of prepared system in the management of DNCB induced dermatitis. Method: Nanolipoidal system was prepared in different combinations with quercetin, L-α phosphatidylcholine (SPC) and ethanol and characterized for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, percentage drug release, skin retention and skin permeation. Selected batches were further incorporated into Carbopol 934 base gel. The vesicles were in size range 324.19-359 nm while polydispersity index (PDI) ranges from 0.241-0.554 and for zeta potential, it was from -26.33 to -39.3 nm. Entrapment efficiency was from 23.77-94.68 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin up to 45.23 µm which was significantly higher than the rhodamine solution (10 µm). In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed a marked decrease in amount of inflammatory cell nucleus in mice treated with quercetin loaded ethosomal gel followed by 76.13% decrease in-ear swelling and ear mass respectively in morphology study. The conventional marketed formulation showed a nominal decrease in epidermal thickness. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Results: The optimized formulation F6 with SPC and ethanol in the ratio of 20:80 displayed the highest drug content and entrapment efficiency of 94.68±1.14%. PDI was 0.241±0.11 and skin retention 7.7%. Batch F6 with vesicle size and zeta potential of 324.9±19 nm and -26.33 mV, respectively, was incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spreadability, in vitro, ex vivo release study, and kinetics study and in vivo studies. Conclusion: The present study revealed that the developed ethosomal gel can be used for enhanced delivery of Quercetin via skin. The in vitro studies indicated that the gel serves as an efficient carrier for Quercetin. It showed its effectiveness in the management of dermatitis. Further, Quercetin loaded nanoethosomal gel formulation can be viewed as a promising drug delivery system for the management of dermatitis.

Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study

Background: Andrographolide is a phytoconstituent with anti-inflammatory activity, however, the compound’s poor oral bioavailability has hindered its effective formulation for oral administration. This study, therefore, aims to develop an ethosome for improving andrographolide penetration through the transdermal delivery system. Methods: This study developed 3 ethosome formulas with different andrographolide-phospholipid weight ratios (1:8, 1:9; 1:10), using the thin-layer dispersion-sonication method. Subsequently, the ethosomes were evaluated for particle size, polydispersity index, zeta potential, morphology, as well as entrapment efficiency, and incorporated into a gel dosage form. Subsequently, an in vitro penetration study was performed using Franz diffusion cells for 24 hours and the stability of the gels at 5 ± 2°C, 30 ± 2°C, and 40 ± 2°C, were studied for 3 months. Results: The results showed the optimal formula was E2, a 1:9 weight ratio formula of andrographolide and phospholipid. Based on the transmission electron micrograph, E2 possessed unilamellar, as well as spherical-shaped vesicles, and exhibited superior characteristics for transdermal delivery, with a particle size of 89.95 ± 0.75 nm, polydispersity index of 0.254 ± 0.020, a zeta potential of -39.3 ± 0.82 mV, and entrapment efficiency of 97.89 ± 0.02%. Furthermore, the cumulative andrographolide penetration and transdermal flux for the ethosomal gel of E2 (EG2) were 129.25 ± 4.66 µg/cm2 and 5.16 ± 0.10 µg/cm2/hours, respectively. All the ethosomal gel formulations exhibited improved penetration enhancement of andrographolide, compared to the nonethosomal formulations. Also, the andrographolide levels in the ethosomal and nonethosomal gels after 3 months ranged from 98.13 to 104.19%, 97.93 to 104.01%, and 97.23 to 102.26% at storage temperatures of 5 ± 2°C, 30 ± 2°C/RH 65% ± 5%, and 40 ± 2°C/RH 75% ± 5%, respectively. Conclusions: This study concluded that encapsulation into ethosome enhances andrographolide delivery through the skin.

Brucine-Loaded Ethosomal Gel: Design, Optimization, and Anti-inflammatory Activity.

Brucine, one of the natural medications obtained from Nux vomica seeds, is used as an anti-inflammatory drug. Several investigations were performed to overcome its drawbacks, which will affect significantly its pharmaceutical formulation. The goal of the current investigation was to design, optimize, and evaluate the anti-inflammatory performance of BRU ethosomal gel. Brucineethosomal formulations were prepared using thin film hydration method and optimized by central composite design approach using three independent variables (lecithin concentration, cholesterol concentration, and ethanol percentage) and three response variables (vesicular size, encapsulation efficiency, and skin permeation). The optimized formulation was examined for its stability and then incorporated into HPMC gel to get BRU ethosomal gel. The obtained BRU-loaded ethosomal gel was evaluated for its physical properties, in vitro release, and ex vivo permeation and skin irritation. Finally, carrageenan-induced rat hind paw edema test was adopted for the anti-inflammatory activity. The developed BRU ethosomal gel exhibited good physical characteristics comparable with the conventional developed BRU gel. In vitro release of BRU from ethosomal gel was effectively extended for 6h. Permeation of BRU from ethosomes was significantly higher than all formulations (p < 0.05), since it recorded steady state transdermal flux value 0.548 ± 0.03μg/cm2h with enhancement ratio 2.73 ± 0.23. Eventually, BRU ethosomal gel exhibited potent anti-inflammatory activity as manifested by a significant decrease in rat hind paw inflammation following 24h. In conclusion, the study emphasized the prospective of ethosomal gel as a fortunate carrier for intensifying the anti-inflammatory effect of Brucine.

In Vitro Assessment of Herbal Topical Ethosomal Gel Formulation for the Treatment of Acne vulgaris

Anti-acne herbal formulations are utilized for the treatment of acne vulgaris with the additional benefit of not creating adverse effects, unlike synthetic drugs. Phytoconstituents present in methanolic extracts of Glycyrrhiza glabra have antibacterial and antioxidant properties. An approved UV spectrophotometer confirmed the presence of glycyrrhizin in these extracts. Extracts loaded with Carbopol 940 were utilized for the preparation of herbal drug-loaded ethosomal gel formulations (EF1, EF2, and EF3) at various times and followed the assessment of ethosomal gel formulation. The evaluation of ethosomal gel formulation done by pH, viscosity, spreadability, texture analysis, differential scanning calorimetry, FT-IR spectral analysis, in vitro drug release study, and antioxidant activity against Propionibacterium acnes. Herbal ethosomal gel formulation demonstrated antibacterial potential and was additionally assessed for skin permeation by gamma scintigraphy utilizing hydrophilic radiotracer 99mTc-DTPA and lipophilic radiotracer 99mTc-MIBI. Significant permeation (1.3 μg/mg) was seen with a hydrophilic radiotracer named 99mTc-DTPA-PHF and this proposed that the formulation was equipped with sustained drug delivery for the treatment of moderate to an extreme type of acne.

Ethosomes-based gel formulation of karanjin for treatment of acne vulgaris: in vitro investigations and preclinical assessment.

The online version contains supplementary material available at 10.1007/s13205-021-02978-3.

Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer.

Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.