Predicting Peptide Permeability Across Diverse Barriers: A Systematic Investigation.

Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R2) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

Development of a novel human stratum corneum mimetic phospholipid -vesicle-based permeation assay models for in vitro permeation studies.

OBJECTIVES: To develop and evaluate a novel human stratum corneum (SC) mimetic phospholipid vesicle-based permeation assay (PVPASC) model for in vitro permeation studies. SIGNIFICANCE: Due to the increasing restrictions on the use of human and animal skins, artificial skin models have attracted substantial interest in pharmaceuticals and cosmetic industries. In this study, a modified PVPASC model containing both SC lipids and proteins was developed. METHODS: The PVPASC model was optimized by altering the lipid composition and adding keratin in the formulation of large liposomes. The barrier properties were monitored by measuring the electrical resistance (ER) and permeability of Rhodamine B (RB). The modified PVPASC model was characterized in terms of the surface topography, solvent influence and storage stability. The permeation studies of the active components in Compound Nanxing Zhitong Plaster (CNZP) were performed to examine the capability of PVPASC in the application of skin penetration. RESULTS: The ER and Papp values of RB obtained from the optimized PVPASC model indicated a similar barrier property to porcine ear skin. Scanning electron microscope analysis demonstrated a mimic 'brick-and-mortar' structure. The PVPASC model can be stored for three weeks at -20 °C, and withstand the presence of different receptor medium for 24 h. The permeation studies of the active components demonstrated a good correlation (r2 = 0.9136) of Papp values between the drugs' permeation through the PVPASC model and porcine ear skin. CONCLUSION: Keratin contained composite phospholipid vesicle-based permeation assay models have been proven to be potential skin tools in topical/transdermal permeation studies.

Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival fibroblasts cells.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic ß cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.

Methyl ketone production by Pseudomonas putida is enhanced by plant-derived amino acids.

Plants are an attractive sourceof renewable carbon for conversion to biofuels and bio-based chemicals. Conversion strategies often use a fraction of the biomass, focusing on sugars from cellulose and hemicellulose. Strategies that use plant components, such as aromatics and amino acids, may improve the efficiency of biomass conversion. Pseudomonas putida is a promising host for its ability to metabolize a wide variety of organic compounds. P. putida was engineered to produce methyl ketones, which are promising diesel blendstocks and potential platform chemicals, from glucose and lignin-related aromatics. Unexpectedly, P. putida methyl ketone production using Arabidopsis thaliana hydrolysates was enhanced 2-5-fold compared with sugar controls derived from engineered plants that overproduce lignin-related aromatics. This enhancement was more pronounced (~seven-fold increase) with hydrolysates from nonengineered switchgrass. Proteomic analysis of the methyl ketone-producing P. putida suggested that plant-derived amino acids may be the source of this enhancement. Mass spectrometry-based measurements of plant-derived amino acids demonstrated a high correlation between methyl ketone production and amino acid concentration in plant hydrolysates. Amendment of glucose-containing minimal media with a defined mixture of amino acids similar to those found in the hydrolysates studied led to a nine-fold increase in methyl ketone titer (1.1 g/L).

Near-infrared light-responsive nanoparticles for improved anticancer efficacy through synergistic chemo-photothermal therapy.

Combined treatment is more effective than single treatment against most forms of cancer. The synergistic chemo-thermotherapy mediated by nanoparticles has superior advantages of lesser adverse effects as a promising cancer therapy modality. In this study, we report a theranostic carrier system co-encapsulating Doxorubicin (DOX) and Indocyanine green (ICG) into the D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS). Full physicochemical characterization studies of the DOX/ICG-loaded TPGS nanoparticles (TNPs) are performed. TNPs have a mean size around 60 nm with superior photostability, and entrapment efficiency of drugs in TNPs was 75.0% for ICG and 68.3% for DOX. TNPs also exhibit a longer sustained release with around 63% of the entrapped drug in 24 h. In vitro studies, TNPs could effectively enhance cellular uptake of DOX and ICG, which permitted high therapeutic efficacy against cancer cells. Further, we investigate antitumor efficacy of TNPs along with its impact on major organs in vivo, TNPs also exhibit a complete inhibition of tumor growth and minimal side effects after irradiation. Collectively, these results suggest that near-infrared light-responsive TNPs can further enhance antitumor effects by synergistic chemo-photothermal therapy.

Development of phospholipid vesicle-based permeation assay models capable of evaluating percutaneous penetration enhancing effect.

OBJECTIVES: The phospholipid vesicle-based permeation assay (PVPA) model has recently been introduced as an in vitro model which can mimic stratum corneum (SC) barriers to estimate the skin permeability of drugs. The aim of this study was to evaluate whether the PVPA model was suitable for the evaluation of penetration enhancing effect of skin penetration enhancers (PE). METHODS: The PVPA model was optimized by changing the lipid composition of both small liposomes (SL), and large liposomes (LL). The barrier properties of the PVPA model were monitored by electrical resistance and permeability measurement of the fluorescent marker Rhodamine B (RB). Then the permeation studies of the five active compounds with different physicochemical properties, namely, ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, and tetrahydropalmatine, were performed directly on PVPA model to evaluate the penetration enhancing effect of menthol. RESULTS AND DISCUSSIONS: The enhancement ratio (ER) ranking of the five active compounds observed using the optimized PVPA model was in accordance with what observed with Franz diffusion cell device using porcine ear skin. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis of PVPA model and porcine ear skin after treatment with menthol has shown similar mechanism of menthol which perturbs the SC lipid arrangement and extracts the SC lipids. CONCLUSIONS: In summary, the optimized PVPA model was used for the first time for the evaluation of the permeation enhancing effect. The optimized PVPA model has shown potential to be applied in a more standardized, cheaper, and ethical way for the screening of PE.

Absorption Characteristics and Environmental Significance of Dissolved Organic Matter in Lake Dongping.

As an important water source in Shandong Province, Lake Dongping is one of the most important inland lakes to South-to-North Water Diversion East Route Project. We tried to provide the basis for real-time monitoring of water quality mutation by using CDOM absorption characteristics. The average values of CDOM absorption coefficients [a(280)，a(350)，a(440)] were (12.90±1.17)，(3.11±0.40) and (0.65±0.09) m-1. a(440) had linear relationships with total nitrogen (p<0.01), total phosphorus (p<0.001), dissolved organic carbon (p<0.001), chemical oxygen demand (p<0.001), Chlorophyll a (p<0.001), which can be used to estimate the water quality parameters. The results showed that CDOM absorption coefficient reflects the nutritional status of Lake Dongping, which is close to eutrophication level. There was an obvious decrease of CDOM absorption coefficients from river mouth of Dawen River to lake center and then to the outlets of lake. This illustrated that terrestrial input is the main source of nutrients and pollutants in Lake Dongping.

[In vitro transdermal permeation and penetration properties for transfersomes of brucine].

To prepare the liposomes and transfersomes of brucine, characterize their pharmaceutical properties, and compare their in vitro transdermal permeation properties. The liposomes and transfersomes of brucine were prepared by ammonium sulfate gradient method to investigate their pharmaceutical properties such as the particle size, encapsulation efficiency and deformation. The transdermal permeation properties in vitro of liposome and transfersomes from different prescriptions were compared by using modified Franz-diffustion cells with rat skin as the transdermal barrier. The results showed that the particle size of liposomes and transfersomes for brucine ranged from 100 nm to 150 nm, with even distribution for particle size. As compared with the soybean phosphatidylcholine (SPC) transfersomes, the encapsulation efficiency of complex phospholipid transfersomes was significantly improved. The deformation index of complex phospholipid transfersomes in brucine was 2.09 times and 1.76 times as much as SPC liposomes and SPC transfersomes respectively. The steady state flux of complex phospholipid transfersomes was 3.43 times and 1.41 times as much as SPC liposomes and SPC transfersomes. The steady state flux of the physical mixture of brucine and blank complex phospholipid transfersomes was 2.20 times as much as brucine solution. The concentration of complex phospholipid had effect on transdermal permeation of blank transfersomes. In conclusion, as compared with liposomes, the permeation behavior of transfersomes was significantly improved; complex phospholipid technology can improve the membrane phase behavior of transfersomes, and further improve the deformation index and transdermal flux of transfersomes; in addition, blank transfersomes have promoting effect on transdermal absorption of brucine.

Polymer nanoparticles based on pyrene-functionalized poly(acrylic acid) for controlled release under photo and pH stimulation.

A novel photo and pH-responsive amphiphilic pyrene-functionalized polymer is synthesized by the esterification reaction between poly(acryloyl chloride) and pyrenemethanol and subsequent hydrolysis of the unreacted acylchloride groups. This random copolymer consists of hydrophobic pyrene-containing acrylate units and hydrophilic acrylic acid units, which can self-assemble into nanoparticles in water. Under UV irradiation, the nanoparticles can be disrupted with decreasing particle number resulted from the photolysis of pyrenylmethyl esters, where the hydrophobic segments are converted to hydrophilic acrylic acids; at low pH, the acrylic acid segments are protonated and collapsed, thus the nanoparticles will be shrunk and aggregated; at high pH, the nanoparticles change to fractal structures owing to the aggregation of partially dissociated nanoparticles and the subsequent structural reorganization of the clusters. The controlled release of Nile Red from the nanoparticles stimulated by photo and pH separately and synergistically is demonstrated. The nanoparticles self-assembled from the dual-stimuli-sensitive polymer can be used as a new nanocarrier and find their applications in delivery system.

Polymer nanoparticles for controlled release stimulated by visible light and pH.

Polymer nanoparticles are prepared by self-assembly of visible light and pH sensitive perylene-functionalized copolymers which are synthesized by quaternization between 1-(bromomethyl)perylene and the dimethylaminoethyl units of poly(dimethylaminoethyl methacrylate) (PDMAEMA). The perylene-containing polymethacrylate segments afford the system visible light responsiveness and the unquaternized PDMAEMA segments afford the system pH responsiveness. The self-assembled nanoparticles exhibit a unique dual stimuli response. They can be photocleaved under visible light irradiation, shrunken to smaller nanoparticles at high pH, and swollen at low pH. The structural change endows the nanoparticle with great potential as a sensitive nanocarrier for controlled release of Nile Red and lysozyme under this stimulation. The visible light responsiveness and synergistic effect on the release of loaded molecules with the dual stimulation may obviate the need for harsh conditions such as UV light or extreme pH stimulation, rendering the system more applicable under mild conditions.

High-efficiency conversion of corn bran to ethanol at 150 L scale.

Fractionated corn bran was processed to maximize ethanol production from starch, cellulose, and xylan. After various bench-scale experiments, an optimized process with dilute acid pretreatment (1.5 % w/w H2SO4) at 90 °C for 60 min was utilized followed by enzymatic hydrolysis using cellulase and hemicellulase for 48 hr. After simultaneous saccharification (regarding starch) and fermentation at 150 L using an engineered yeast, which consumes both glucose and xylose to make ethanol, the 86 % total sugar conversion yield was achieved, including conversions of 95 % for starch, 77 % for cellulose and 77 % for xylan. Also, an accurate mass balance was formulated for ethanol-producing carbohydrates including starch, cellulose, and xylan from feedstock to final ethanol. A highly efficient process of converting corn fiber to ethanol was successfully scaled up to 150 L.

Photoswitched protein adsorption on electrostatically self-assembled azobenzene films.

Photoresponsive polymeric films fabricated by a facile electrostatic self-assembly technique are utilized to switch protein adsorption by light irradiation. The introduction of SiO(2) nanoparticles on the substrate results in a large reversible change of both wettability and protein adsorption.

Numerical Analysis of Flexural Behavior of Prestressed Steel-Concrete Continuous Composite Beams Based on BP Neural Network.

Prestressed steel-concrete continuous composite beam (PCCB) is a kind of beam, which makes reinforced concrete slab and steel beam bear load and coordinate deformation through connectors such as studs. Prestressed steel-concrete continuous composite beam is a kind of transverse load-bearing composite member formed by prestressed technology on the basis of ordinary composite beam. Aiming at the flexural behavior of prestressed steel-concrete continuous composite beams, a three-dimensional finite element numerical analysis model is established, and the whole process of the test is simulated based on BP neural network. The calculated results are in good agreement with the test. Using this model, the mechanical deformation performance of prestressed steel-concrete continuous composite beam is further analyzed, and the effects of some parameters (steel beam strength grade, concrete strength grade, concrete slab thickness, and transverse reinforcement ratio) on the flexural performance of prestressed steel-concrete continuous composite beam are discussed, which provides a reference basis for engineering design.

Multifunctional MnO2/Ag3SbS3 Nanotheranostic Agent for Single-Laser-Triggered Tumor Synergistic Therapy in the NIR-II Biowindow.

Regulating the level of reactive oxygen species (ROS) in a tumor is an efficient and innovative anticancer strategy. However, the therapeutic efficacy of ROS-based therapies, such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), offers finite outcomes due to the oxygen dependence and limited concentration of hydrogen peroxide (H2O2) and overexpression of glutathione (GSH) within the tumor microenvironment (TME), so a single therapeutic strategy is insufficient to completely eliminate tumors. Therefore, we demonstrated an omnipotent nanoplatform MnO2/Ag3SbS3 (abbreviated as MA) with strong optical absorbance in the NIR-II biowindow and oxygen self-sufficient ROS-mediated ability, which not only relieves tumor hypoxia significantly but also enhances the photothermal therapy (PTT)/PDT/CDT efficacy. By 1064 nm laser irradiation, MnO2/Ag3SbS3 nanoparticles (NPs) reveal a favorable photothermal conversion efficiency of 23.15% and achieve a single-laser-triggered NIR-II PTT/PDT effect, resulting in effective tumor elimination. Once internalized into the tumor, MnO2/Ag3SbS3 NPs will be degraded to Mn2+ and Ag3SbS3. The released Ag3SbS3 NPs as a NIR-II phototherapy agent could be utilized for photoacoustic imaging-guided NIR-II PDT/PTT. Mn2+ could be used as a Fenton-like catalyst to continuously catalyze endogenous H2O2 for generating highly virulent hydroxyl radicals (•OH) for CDT and O2 for PDT, enhancing the efficiency of PDT and CDT, respectively. Meanwhile, Mn2+ realizes magnetic resonance imaging-guided accurate tumor therapy. Moreover, the MnO2/Ag3SbS3 NPs could deplete intracellular GSH in TME to promote oxidative stress of the tumor, further strengthening ROS-mediated antitumor treatment efficacy. Overall, this work presents a distinctive paradigm of TME-responsive PDT/CDT/PTT in the second near-infrared biowindow by depleting GSH and decomposing H2O2 for efficient and precise cancer treatment.

Effect of linear accelerator carbon fiber couch on radiotherapy dose.

This study aimed to explore the effect of carbon fiber couch on radiotherapy dose attenuation and gamma pass rate in intensity-modulated radiotherapy (IMRT) plans. A phantom inserted with an ionization chamber was placed at different positions of the couch, and the dose was measured by the chamber. Under the same positioning, the phantom dose was calculated using the real and virtual couch images, and the difference in the planned dose of radiotherapy was compared. Ten clinical IMRT plans were selected as dose verification data, and the gamma pass rates were compared between couch addition and non-addition conditions. When the radiation field was near 110° and 250°, the measured value attenuation coefficient of the ionization chamber at the joint of the couch was up to 34%; the attenuation coefficient of the treatment couch from the actual couch image calculated using the treatment planning system (TPS) was up to 33%; the attenuation coefficient of the virtual couch calculated using the TPS was up to 4.0%. The gamma pass rate of the dose verification near gantry angles 110° and 250° was low, and that of the joint could be lower than 85% under the condition of 3%/3 mm. The gamma pass rates of the radiation field passing through the couch were all affected. The dose was affected by the radiation field passing through the couch, with the largest effect when passing through the joint part of the treatment couch, followed by that of the main couch plate and extension plate. When the irradiation field passed through the joint and near 110° and 250° of the main couch, the dose difference was large, making it unsuitable for treatment.

[Growth and migration of umbilical cord mesenchymal stem cells on polycarbonate membrane with different pore sizes].

OBJECTIVE: To observe the growth and migration of human umbilical cord mesenchymal stem cells (hUCMSCs) on polycarbonate membrane with different pore sizes and explore the criteria of selecting optimal Transwell insert for indirect co-culture to induce the differentiation of hUCMSCs. METHODS: hUCMSCs were isolated in vitro and then expanded in culture medium. After the treatment of mitomycin C, the cells were seeded on porous membranes of 6-well-dish Transwell inserts with different pore sizes of 0.4, 3.0 and 8.0 µm respectively. After culturing for 7 days, the cells were observed and counted on the bottom of each porous membrane. Then the calculation of migration ratio was performed. The growth and migration of hUCMSCs on porous membranes were also examined under scanning electron microscope (SEM). RESULTS: The migration ratios of hUCMSCs on membranes of 0.4, 3.0 and 8.0 µm pore sizes were 0, 1.8% and 8.0% respectively. The migration ratio of cells on 0.4 µm pore size membrane was statistically different from that of the other two pore size groups (P < 0.01). Under SEM, a small portion of cells were growing on the bottoms of membranes and moving through the pores. But there was no cell movement through 0.4 µm pore size membrane. CONCLUSIONS: hUCMSCs can migrate through the polycarbonate membranes of 3.0 µm and 8.0 µm pore sizes but not through the 0.4 µm one. Thus both sides of polycarbonate membrane of 0.4 µm pore size may be used for close indirect co-culture to induce the differentiation of hUCMSCs.

PharmSD: A novel AI-based computational platform for solid dispersion formulation design.

Solid dispersion is an effective way to improve the dissolution and oral bioavailability of water-insoluble drugs. To obtain an effective solid dispersion formulation, researchers need to evaluate a series of important properties of the designed formulation, including in vitro dissolution and physical stability of solid dispersion. It is usually time-consuming and labor-intensive to explore these properties by traditional experimental methods. However, the development of machine learning technology provides a powerful way to solve such problems. By using advanced machine learning algorithms, we established a series of robust models and finally formed a systematic strategy to assist the formulation design. Based on these works, we developed a new formulation prediction platform of solid dispersion: PharmSD. This platform provides efficient functionalities for the prediction of physical stability, dissolution type and dissolution rate of solid dispersion independently. Then, a virtual screening pipeline can be produced by considering those prediction results as a whole, which enables users to filter different kinds of drug-polymer combinations in various experimental situations and figure out which combination could form the best formulation. Moreover, it also provides two tools that enable researchers to evaluate the application domain of models and calculate the similarity of dissolution curves. PharmSD is expected to be the first freely available web-based platform that is fully designed for the formulation design of solid dispersion driven by machine learning. We hope this platform could provide a powerful solution to assist the formulation design in the related research area. It is available at: http://pharmsd.computpharm.org.

A natural anthocyanin-based multifunctional theranostic agent for dual-modal imaging and photothermal anti-tumor therapy.

Nowadays, cancer is one of the most serious diseases threatening the health of human beings, and imaging-guided photothermal therapy (PTT) is rapidly emerging as a potent oncotherapy strategy due to its unique advantages of high efficiency, noninvasiveness, visualization, and accuracy. In this study, a multifunctional nanoplatform based on gadolinium ion chelated natural anthocyanins (ACNs) is reported, which can be used not only as an excellent photoacoustic/magnetic resonance (PA/MR) dual-modal contrast agent but also for imaging-guided tumor PTT. The nanoparticles obtained have a suitable size, good dispersity, and physiological stability. The excellent biocompatibility and remarkable photothermal effect of the nanoparticles in vitro were demonstrated by CCK-8 assays and co-staining experiments. Moreover, the magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) results obtained in vivo showed that the nanoparticles were ideal dual-modal contrast agents whether given by intravenous or intratumoral injection. After intratumoral injection, the dual-modal PAI/MRI was used for determining the maximum diffusion time of the probe in the tumor site to guide laser treatment, achieving complete tumor elimination without normal tissue injury. Importantly, ACN is a natural compound extracted from black carrots, possessing native biocompatibility and biodegradability, which was further proved by the results of the detailed safety evaluation. Overall, the as-prepared nanoparticles displayed significant tumor diagnosis and treatment effects while mitigating biosafety concerns, and thus this was found to be a promising nanotherapeutic method for cancer treatment.

Nanocellulose-lysozyme colloidal gels via electrostatic complexation.

Biohybrid colloids were fabricated based on electrostatic complexation between anionic TEMPO-oxidized cellulose nanofibrils (TO-CNF) and cationic hen egg white lysozyme (HEWL). By altering the loading of HEWL, physical colloidal complexes can be obtained at a relatively low concentration of TO-CNF (0.1 wt%). At neutral pH, increasing the HEWL loading induces an increase in charge screening, as probed by zeta-potential, resulting in enhanced TO-CNF aggregation and colloidal gel formation. Systematic rheological testing shows that mechanical reinforcement of the prepared biohybrid gels is easily achieved by increasing the loading of HEWL. However, due to the relatively weak nature of electrostatic complexation, the formed colloidal gels exhibit partial destruction when subjected to cyclic shear stresses. Still, they resist thermo-cycling up to 90 °C. Finally, the pH responsiveness of the colloidal complex gels was demonstrated by adjusting pH to above and below the isoelectric point of HEWL, representing a facile mechanism to tune the gelation of TO-CNF/HEWL complexes. This work highlights the potential of using electrostatic complexation between HEWL and TO-CNF to form hybrid colloids, and demonstrates the tunability of the colloidal morphology and rheology by adjusting the ratio between the two components and the pH.

Development of curcumin-loaded composite phospholipid ethosomes for enhanced skin permeability and vesicle stability.

Ethosomes are widely applied as the carriers for the transdermal delivery of hydrophobic and hydrophilic drugs. Herein, curcumin-loaded ethosomes (CE) with different phospholipid composition were formulated and thoroughly compared. A significant interaction between the unsaturated phosphatidylcholine (PC) and saturated hydrogenated phosphatidylcholine (HPC) was found by molecular simulation and differential scanning calorimetry (DSC), which led to the reduction of PC peroxidation with the presence of HPC. Subsequently, the composite phospholipid ethosomes containing curcumin were prepared for the first time to evaluate their properties in comparison with the conventional ethosomes composed of PC (CE-P) or HPC (CE-H). CE with PC/HPC ratio of 1:1 (CE-P1H1) with the best vesicle stability and flexibility significantly decreased the uptake by HaCaT cells compared to CE-H and free curcumin, indicating reduced skin cell toxicity. Compared with free curcumin, CE-P1H1 had the highest transdermal efficiency (p < 0.001), followed by CE-P (p < 0.05), partly due to the fact that CE-P1H1 could disturb lipid domain of stratum corneum (SC). Moreover, CE-P1H1 was found to promote curcumin for deep penetration of the skin via the hair follicles route. Our study has shown that using composite phospholipid ethosomes as lipid vesicular carriers could enhance transdermal penetration of drugs and increase in the vesicle stability.