Engineered plant extracellular vesicles for natural delivery across physiological barriers.

Extracellular vesicles (EVs) are nanoscale luminal vesicles that participate in the information transfer of proteins, nucleic acids, and lipids between cells, thereby playing a role in the treatment of diseases and the delivery of nutrients. In recent years, plant-derived EVs (PDEVs) containing bioactive compounds have attracted increasing interest due to their better biocompatibility and lower cytotoxicity in healthy tissues. In the biomedical field, PDEVs have been used as cargo carriers to achieve various functions through engineering modification techniques. This review focuses on the biogenesis, isolation, and identification of PDEVs. We discuss the surface functionalization of PDEVs to enhance therapeutic efficacy, thereby improving their efficiency as a next-generation drug delivery vehicle and their feasibility to treat diseases across the physiological barriers, while critically analyzing the current challenges and opportunities.

Tetramethylpyrazine-loaded liposomes surrounded by hydrogel based on sodium alginate and chitosan as a multifunctional drug delivery System for treatment of atopic dermatitis.

Tetramethylpyrazine (TMP) has low bioavailability due to its fast metabolism and short half-life, which is not conducive to transdermal treatment of atopic dermatitis (AD). Therefore, in this study, TMP was encapsulated into liposomes (Lip) by film dispersion method, and then the surface of Lip was modified by sodium alginate (ALG) and chitosan (CS). The tetramethylpyrazine-loaded liposomes in sodium alginate chitosan hydrogel called T-Lip-AC hydrogel. In vitro experiments, we found that T-Lip-AC hydrogel not only had the antibacterial effect of CS, but also enhanced the anti-inflammatory and antioxidant effects of TMP. In addition, T-Lip-AC hydrogel could also provide a moist healing environment for AD dry skin and produce better skin permeability, and can also achieve sustained drug release, which is conducive to the treatment of AD. The lesions induced by 1-chloro-2,4-dinitrobenzene were used as the AD lesions model to test the therapeutic effect of the T-Lip-AC hydrogel on AD in vivo. The studies have showed that T-Lip-AC hydrogel could effectively promote wound healing. Therefore, we have developed a T-Lip-AC hydrogel as multifunctional hydrogel drug delivery system, which could become an effective, safe and novel alternative treatment method for treating AD.

Antioxidant Activity of Quercetin-Containing Liposomes-in-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema.

Cutaneous eczema is a kind of skin disease is characterized by inflammation. The main manifestations are various types of dermatitis, eczema, and urticaria. There are usually complications such as erythema, blisters, and epidermal peeling. The quercetin might have a therapeutic effect on cutaneous eczema due to its favorable antioxidant activity and anti-inflammatory effects. Currently, there are few studies on transdermal administration of antioxidant drugs for the treatment of cutaneous eczema. The aim of this study was to prepare quercetin-containing liposomes-in-gel (QU-LG), its antioxidant properties were evaluated, and it was used in the skin of mice suffering from dermal eczema to see if it had preventive and therapeutic effects in an attempt to make it a new option for the treatment of cutaneous eczema. QU-LG was prepared by the injection method to form the quercetin-containing liposomes (QU-L) and evenly dispersed in the natural dissolution of carboxymethylcellulose sodium (1%, CMC-Na). The release of QU-LG across the dialysis membranes was up to 30% and clearance of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was 65.16 ± 3.513%. In anti-oxidation assay QU-LG inhibited malondialdehyde (MDA) production in liver better than the commercially available drug dexamethasone acetate cream. Compared with untreated mice, mice treated with QU-LG showed a statistically significant reduction in dermatopathologic symptoms. The results suggested that QU-LG had good antioxidant activity in vivo and in vitro and could be used for the prevention and treatment of cutaneous eczema.

In situ imaging of signaling molecule carbon monoxide in plants with a fluorescent probe.

Carbon monoxide (CO) is a recently discovered gasotransmitter. In animals, it has been found that endogenously produced CO participates in the regulation of various metabolic processes. Recent research has indicated that CO, acting as a signaling molecule, plays a crucial regulatory role in plant development and their response to abiotic stress. In this work, we developed a fluorescent probe, named COP (carbonic oxide Probe), for the in situ imaging of CO in Arabidopsis thaliana plant tissues. The probe was designed by combining malononitrile-naphthalene as the fluorophore and a typical palladium-mediated reaction mechanism. When reacted with the released CO, COP showed an obvious fluorescence enhancement at 575 nm, which could be observed in naked-eye conditions. With a linear range of 0-10 µM, the limit of detection of COP was determined as 0.38 µM. The detection system based on COP indicated several advantages including relatively rapid response within 20 min, steadiness in a wide pH range of 5.0-10.0, high selectivity, and applicative anti-interference. Moreover, with a penetration depth of 30 µm, COP enabled 3D imaging of CO dynamics in plant samples, whether it was caused by agent release, heavy metal stress, or inner oxidation. This work provides a fluorescent probe for monitoring CO levels in plant samples, and it expands the application field of CO-detection technology, assisting researchers in understanding the dynamic changes in plant physiological processes, making it an important tool for studying plant physiology and biological processes.

Imaging of a novel ratio γ-glutamyl transpeptidase fluorescent probe in living cells and biopsies.

Herein, a novel fluorescent probe, GTP, was developed for monitoring the GGT (γ-glutamyl transpeptidase) level in living cells and biopsies. It consisted of the typical recognition group γ-Glu (γ-Glutamylcysteine) and the fluorophore (E)-4-(4-aminostyryl)-1-methylpyridin-1-ium iodide. With a ratio response between the signal intensity at 560 nm and 500 nm (RI560/I500), it could be important complement for the turn-on ones. With the linear range of 0-50 U/L, the limit of detection was calculated as 0.23 µM. The detection system showed the strongest response near pH 7.4, and exhibited steady fluorescence signals for at least 48 h. With high selectivity, good anti-interference and low cytotoxicity, GTP was suitable for physiological applications. By monitoring the GGT level with the ratio values in the green and blue channels, the probe GTP could distinguish cancer cells from normal cells. Furthermore, in the mouse tissues and humanization tissue samples, the probe GTP could also recognize the tumor tissues from the normal ones.

Design and Evaluation of Paeonol-Loaded Liposomes in Thermoreversible Gels for Atopic Dermatitis.

Paeonol (PAE) is a hydrophobic drug. In this study, we encapsulated paeonol in a lipid bilayer of liposomes (PAE-L), which delayed drug release and increased drug solubility. When PAE-L was dispersed in gels (PAE-L-G) based on a poloxamer matrix material for local transdermal delivery, we observed amphiphilicity, reversible thermal responsiveness, and micellar self-assembly behavior. These gels can be used for atopic dermatitis (AD), an inflammatory skin disease, to change the surface temperature of the skin. In this study, we prepared PAE-L-G at an appropriate temperature for the treatment of AD. We then assessed the gel's relevant physicochemical properties, in vitro cumulative drug release, and antioxidant properties. We found that PAE-loaded liposomes could be designed to increase the drug effect of thermoreversible gels. At 32 °C, PAE-L-G could change from solution state to gelatinous state at 31.70 ± 0.42 s, while the viscosity was 136.98 ± 0.78 MPa.S and the free radical scavenging rates on DPPH and H2O2 were 92.24 ± 5.57% and 92.12 ± 2.71%, respectively. Drug release across the extracorporeal dialysis membrane reached 41.76 ± 3.78%. In AD-like mice, PAE-L-G could also relieve skin damage by the 12th day. In summary, PAE-L-G could play an antioxidant role and relieve inflammation caused by oxidative stress in AD.

Ligustrazine as an Extract from Medicinal and Edible Plant Chuanxiong Encapsulated in Liposome-Hydrogel Exerting Antioxidant Effect on Preventing Skin Photoaging.

Long-term sunlight exposure will cause the accumulation of free radicals in the skin and lead to oxidative damage and aging, antioxidant drugs have gradually become the focus of research, but there is little research on antioxidant drugs for percutaneous treatment. The purpose of this study was to prepare ligustrazine hydrochloride (TMPZ)-loaded liposome-hydrogel (TMPZ-LG), evaluate its antioxidant properties, and apply it on the skin of mice to observe whether it had preventive and therapeutic effect on the irradiation under the ultraviolet rays, in an attempt to make it into a new kind of delivery through the skin. TMPZ-LG was prepared by the combination of film dispersion and sodium carboxymethylcellulose (2%, CMC-Na) natural swelling method. The release rates in vitro permeation across the dialysis membrane and ex vivo transdermal had both reached 40%; the scavenging effect of TMPZ-LG on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2 were 65.57 ± 4.13% and 73.06 ± 5.65%; the inhibition rate of TMPZ-LG on malondialdehyde (MDA) production in liver homogenate and anti-low density lipoprotein (LDL) oxidation experiments ex vivo were 15.03 ± 0.9% and 21.57 ± 1.2%. Compared with untreated mice, the skin pathological symptoms of mice coated with TMPZ-LG were significantly reduced after ultraviolet irradiation, and there was statistical significance. The results showed TMPZ-LG could exert good antioxidant activity in vitro and ex vivo; therefore, it is feasible to prevent and treat skin oxidation.

A pH-applicative fluorescent probe with long measuring range for monitoring hydrazine in water samples and Arabidopsis thaliana.

In this work, a fluorescent probe, RhodCl-Hz, with pH-applicative capability and long measuring range, was developed to serve the topic on the enrichment process of hydrazine. It was practical due to the clear acid-base boundary and the sectioned linear ranges. With the excitation wavelength of 515 nm and the emission peak at 565 nm, the detecting system was steady. It exhibited a clear cut-off point at pH 7.0 and steady fluorescence signals within the range of 7.0-10.0. As a whole, the linear range of 10.0-500 µM (1.0-50.0 equivalent) was long. The Limit of Detection value was calculated as 0.64 µM. With high selectivity, RhodCl-Hz was applied to suit water samples and biological imaging in both Arabidopsis Thaliana root tips and living MCF-7 cells. The information here might be helpful for revealing the enrichment process of hydrazine.

Study on the controlled release and synergistic anti-oxidant activity in vitro and ex vivo of ligustrazine hydrochloride encapsulated into liposomes.

Ligustrazine with good antioxidant activity is one of the main active components of chuanxiong. We designed ligustrazine hydrochloride-loaded liposomes (LTH-L) by the thin film dispersion method. The particle size and zeta potential of liposomes was 118±10.61nm and -39.3±3.7mV, entrapment efficiency (EE%) was 75.05±10.67%. In vitro permeation across the dialysis membrane, the release rate (R%) of ligustrazine hydrochloride (LTH) and LTH-L were reached 80% and 60%. Ex Vivo transdermal behavior experiment showed the R% of LTH and LTH-L were between 30%-40%, the R% of LTH-L was slightly lower, because liposomes played the role on the sustained and controlled release of LTH. In addition, LTH, LTH-L and BL reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution for two hours, the scavenge rates (SR%) were 55.06±2.73%, 11.3±0.03% and 37.25±1.12% respectively (P<0.001) and the SR% of LTH, LTH-L and BL reacted with H2O2 were 4.13±0.02%, 0.52±0.01% and 75.15±6.10%. The inhibit rate (IR%) of LTH, LTH-L and BL on malondialdehyde (MDA) in liver homogenate were 35.44±1.79%, 1.22±0.01% and 17.92±0.29% (P<0.001), the IR% were 30.82±0.93%, 1.7±0.01% and 25.19±0.60% (P<0.001) in anti-low density lipoprotein (LDL) oxidation experiments, perhaps LTH prepared into LTH-L can play a better antioxidant role.

Interfacial Diffusion of Hydrated Ion on Graphene Surface: A Molecular Simulation Study.

Hydration plays an important role in the diffusion and sieving of ions within nanochannels. However, it is hard to quantitatively analyze the contribution of hydration to the diffusion rates due to the complex hydrogen-bond and charge interactions between atoms. Here, we quantitatively investigated the interfacial diffusion rates of a single hydrated ion with different number of water molecules on graphene surface through molecular dynamics simulation. The simulation results show the ballistic diffusion mode by analyzing the mean-square displacement, and the diffusion rates change nonmonotonically with the hydration number. The potential energy profiles with the changing position of the hydrated ion on graphene surface were further analyzed, which shows the dominant factor for interfacial diffusion changing from ion-graphene interaction to water-graphene interaction as the number of water molecules increases. Besides, it was found that the surface hydrophilicity weakened the influence of hydration number on the diffusion rates of hydrated ion. Finally, the diffusion properties of different hydrated ions on graphene surface were investigated, and the hydrated Li+, Na+, and K+ containing three, four, and five water molecules, respectively, show the fastest diffusion rate. This work demonstrates the interfacial diffusion behavior and mechanism of hydrated ions at the molecular level, which can provide valuable guidance in nanosensors, seawater desalination, and other hydrated ion-related fields.

Investigation on the Preparation, Characteristics, and Controlled Release Model of Paeonol-Loaded Liposome in Carbomer Hydrogel.

OBJECTIVE: Paeonol is a phenolic compounce that is volatile. In order to decrease its volatility and achieve controlled release, paeonol-loaded liposome in carbomer hydrogel was prepared by coating with soybean phospholipid via ethanol injection method and then added into the carbomer hydrogel. METHODS: The quality of paeonol-loaded liposome in carbomer hydrogel was evaluated by the degree of roundness, particle size distribution, zeta potential, entrapment efficiency (filtration method and chitosan neutralization method), viscosity, infrared spectrum, etc. Furthermore, the diffusion from paeonolloaded liposome in hydrogel was studied in vitro. RESULTS: The results showed that the average particle size of paeonol-loaded liposome was about 401 nm, the potential was -17.8 mV, and the entrapment efficiency was above 45%. The viscosity of paeonol- loaded liposome in hydrogel was 23.972×10-3 Pa*s, and the diffusion rate from paeonol-loaded liposome in hydrogel in vitro was obviously slower than that from the other paeonol preparations. CONCLUSION: The conclusions could be drawn that paeonol-loaded liposome in hydrogel was a kind of novel preparation, and its diffusion in vitro had obvious controlled-release characteristics, which further proved that it might improve the bioavailability of paeonol.

Conformation-induced separation of 3-chloropropene from 1-chloropropane through nanoporous monolayer graphenes.

Achieving ultrahigh selectivity for separating paraffin/olefin mixtures with physical and chemical similarity, especially for halohydrocarbons, is a long-standing challenge in high-purity polymer production. We explored three H-saturated nanoporous graphene (NG) membranes with appropriate pore geometries that can achieve the complete exclusion of 1-chloropropane (C3H7Cl) from C3H5Cl during molecular dynamics simulations. Inferred from thermodynamics calculations, C3H5Cl has a lower energy barrier of penetration than C3H7Cl and the NG membranes show preferential adsorption to C3H5Cl, which facilitate the penetration of C3H5Cl through the pores. The conformational energy analysis of the two molecules shows that C3H5Cl has a lower energy penalty to twist to the molecular conformation that nanopores preferred than C3H7Cl, which mainly determines the ultrahigh selectivity for C3H5Cl. We anticipate that the conformation-induced mechanism outlined here can provide a reference to separate paraffin/olefin mixtures with distinctly different conformational energy profiles.

The Controlled Release and Anti-Inflammatory Activity of a Tetramethylpyrazine-Loaded Thermosensitive Poloxamer Hydrogel.

PURPOSE: Tetramethylpyrazine-loaded poloxamer hydrogel materials were studied to achieve the controlled release of tetramethylpyrazine. METHODS: First, hydrogels having different concentrations of poloxamer 407 and poloxamer 188 were prepared. The gelling temperature and viscosity were measured. Second, we investigated the tetramethylpyrazine release rate from the thermosensitive poloxamer hydrogel materials in vitro and ex vivo. Finally, further study of the pharmacological efficacy of the tetramethylpyrazine-loaded thermosensitive poloxamer hydrogel materials was also investigated in vivo. RESULTS: The in vitro, ex vivo and in vivo experimental results showed that the tetramethylpyrazine-loaded poloxamer hydrogel with the appropriate gelling temperature, good adhesion and easy preparation controlled the release of tetramethylpyrazine. CONCLUSIONS: The hydrogel with the suitable nasal temperature and a satisfactory adhesion was selected. The relevant tests were carried out, including the determination of the concentration of drugs in the brain homogenate and the anti-inflammatory test after different modes of administration. So the poloxamer hydrogel was a novel carrier to deliver TMP to pass across the blood brain barrier via nasal administration.

In-situ sludge reduction and carbon reuse in an anoxic/oxic process coupled with hydrocyclone breakage.

The long-term performance of an anoxic-oxic-hydrocyclone (AOH) process with an in-situ hydrocyclone treatment unit in the mixed liquid return line for sludge reduction and carbon reuse has been observed, in comparison with a conventional anoxic-oxic (AO) process. Three parallel side-stream systems, including one AOH25 system with a 25-mm hydrocyclone, one AOH35 system with a 35-mm hydrocyclone and one AO system, were built and fed with real wastewater for a comparative study in a wastewater treatment plant. The results demonstrate that the hydrocyclone in the AOH process was able to break macro-flocs into smaller flocs. And the desorption of the extracellular polymeric substance from return activated sludge (AS) leaded to an average increase of 62.97% and 36.36% in SCOD in the AOH25 and AOH35 system, respectively. In addition, shear forces, centrifugal forces of revolution and flocs' rotation in the hydrocyclone were proposed to be the main influence mechanism of hydrocyclone treatment on AS properties. Compared with the AO process, the SCOD concentration in the effluent of the AOH processes presented a decrease of 12.0 mg/L and the TN was reduced by 21.50% owing to the released carbon sources reuse. Moreover, the sludge production was reduced by 36.81% and 35.92% in the AOH25 and AOH35 process, respectively. By contrast, the AOH25 system was better than the AOH35 system.

Achieving enhanced denitrification via hydrocyclone treatment on mixed liquor recirculation in the anoxic/aerobic process.

This work presents the novel application of hydrocyclones for mixed liquor recirculation (MLR) treatment in the anoxic/aerobic (A/O) process to enhance the denitrification process. An exhaustive investigation on treated activated sludge and A/O effluents was conducted in batch and continuous operation tests. The median diameter of the sludge flocs was decreased from 78.82 µm to 15.77-23.31 µm, and the extracellular polymeric substances (EPS) desorption was observed, thus leading to the release of the soluble chemical oxygen demand (SCOD). A marked increase in the BOD5/TN ratio was consequently achieved, which supplied the carbon source and improved the biodegradability of the MLR. The hydrocyclone treatment also enabled a 7.17% ± 0.93% specific oxygen utilization rate (SOUR) increase at the optimal hydrocyclone intensity of 0.13 MPa, owing to the desorption of positioned microbial secretion from the microorganism cells. The nitrate reductase and nitrite reductase were also improved by 15.13% ± 1.16% and 17.61% ± 1.55%, respectively. The nitrate removal efficiency was enhanced by 13.6%, and the nitrogen oxide gases varied slightly; this behavior was consistent with the variations in the key enzymes involved in denitrification. The A/O process operated in the mode of hydrocyclone-treated MLR, compared with in the conventional mode, resulted in a 15.56% higher TN removal, and the other effluent parameters remained stable. Hydrocyclone disruption is thus a convenient and energy-efficient process with broad implications in denitrification development.

Synthesis, Crystal Structures, Molecular Docking and MAO-B Inhibitory Activity of Transition Metal Complexes Derived from 2-(4-(Pyridin-2-yl)piperazin-1-yl)acetic Acid.

Three new complexes derived from 2-(4-(pyridin-2-yl)piperazin-1-yl)acetic acid (HL), [M(L)2(H2O)2] where M = CuII (1), ZnII (2) and CdII (3), have been synthesized and characterized by IR spectroscopy, elemental analysis and X-ray crystallography. The inhibitory activity of these three complexes against MAO-B was tested in vitro, and the molecular docking experiments were also carried out to rationalize their binding models. Both the experimental and docking simulation results indicated that complex 1 has the best inhibitory activity with IC50 value being 6.5 ± 0.31 µM.

Tetramethylpyrazine-Loaded Hydrogels: Preparation, Penetration Through a Subcutaneous-Mucous-Membrane Model, and a Molecular Dynamics Simulation.

Tetramethylpyrazine (TMP) was extracted from Ligusticum chuanxiong hort. The compound is known to have a variety of medicinal functions; in particular, it is used for the treatment of cerebral ischemic diseases. TMP-loaded hydrogels offer an excellent preparation with the capacity to bypass the blood-brain barrier, allowing treatment of the brain through intranasal administration. We prepared TMP-loaded hydrogels using carbomer 940 and evaluated the release of TMP from the hydrogel. We determined the release rate using Franz-type diffusion cell experiments with a subcutaneous-mucous-membrane model and also by a molecular dynamics (MD) simulation. In general, the former method was more complicated than the latter was. The dynamic behavior of TMP release from the hydrogel was revealed by analysis of the mean square displacement of the trajectory in the MD simulation. The coefficient of TMP diffusion from the hydrogel was calculated at different temperatures (277, 298, and 310 K) by using MD software. The results showed that the coefficient of diffusion increased with an increase in temperature. This trend was observed both experimentally and in the MD simulation. Therefore, the MD simulation was a complementary method to verify the experimental data.

Investigating the passage of tetramethylpyrazine-loaded liposomes across blood-brain barrier models in vitro and ex vivo.

Tetramethylpyrazine (TMP) is a natural product extracted from Rhizoma Chuanxiong. Liposomes are an excellent delivery method that is suitable for the penetration of the blood-brain barrier (BBB). TMP-loaded liposomes are suitable for the treatment of cerebral ischemic diseases. We measured the morphology, particle size, zeta-potential, entrapment efficiency, and content of TMP-loaded liposome. The electrochemical method was adopted to determine entrapment efficiency for the first time. In addition, their diffusion through BBB models, which were built not only by in vitro cell culture but also by the ex vivo mouse subcutaneous-mucous-membrane (mSMM) method, was explored. The results showed that TMP and TMP-loaded liposomes could effectively permeate both BBB models. Therefore, the study indicated that liposomes were a novel carrier that could deliver TMP across the body barrier models and then release TMP slowly.

Retinoic acid liposome-hydrogel: preparation, penetration through mouse skin and induction of F9 mouse teratocarcinoma stem cells differentiation

Retinoic acid (RA), a metabolite of retinol, is one of the most biologically active forms of retinoid and plays vital roles in embryonic development and in the regulation of cell proliferation and differentiation. Knowing that liposomes simulate cell membranes and that hydrogel is an ideal delivery vehicle for topical medicine, liposome-hydrogel is a novel preparation that has synergistic advantages over each component separately. Our objective was to investigate the characteristics of RA liposome-hydrogel. For quality control of the RA-loaded liposomes, we measured their morphology, particle size, Zeta-potential, and entrapment efficiency. Then we determined the viscosity of RA liposome-hydrogel. Next, the diffusion through mouse skin was explored, followed by investigation of the mRNA expression levels of Ker18, REX1, and α-FP using Q-PCR. The results showed that RA liposome-hydrogel penetrates the mouse skin effectively. The permeation rates were: Qn (%) of RA liposome-hydrogel < Qn(%) of RA-loaded liposome < Qn (%) of RA. The mRNA expression levels were dose-dependent and the effective dose decreased between vehicles due to their different release rates. F9 mouse teratocarcinoma stem cells were an ideal model to explore the mechanism of RA liposome-hydrogel in stem cell differentiation.

O ácido retinóico (RA) é um metabolito de retinol. Ele também é uma das formas mais biologicamente ativas de retinóide. Desempenha papel vital no desenvolvimento embrionário e na regulação da proliferação e diferenciação celular. Sabendo-se que lipossomas simulam a membrana das células e que hidrogel é um sistema ideal para o medicamento tópico, o lipossoma-hidrogel é uma nova preparação, que apresenta vantagens sinérgicas em relação a cada um dos componentes separados. Nosso objetivo foi investigar as características de RA lipossoma-hidrogel. A fim de controlar a qualidade do lipossoma carregado com RA, medimos morfologia, tamanho das partículas, potencial zeta e eficiência de retenção. Em seguida, determinou-se a viscosidade de RA lipossoma-hidrogel. Em seguida, avaliou-se a sua difusão através da pele de camundongos, seguida da investigação dos níveis da expressão de mRNA de Ker18, REX e de α-FP, utilizando-se Q-PCR. Os resultados mostraram que RA lipossoma-hidrogel pode penetrar na pele do camundongo de forma eficaz. As taxas de permeação foram: Qn (%) de RA lipossoma-hidrogel<Qn(%) de lipossoma RA- carregado <Qn (%) de RA. Os níveis de expressão de mRNA foram dependentes de dose e a dose efetiva diminuiu entre os veículos devido às diferentes taxas de liberação, As células estaminais de teratocarcinoma F9 de camundongo mostraram-se como modelo ideal para explorar o mecanismo de diferenciaçãode células tronco pelo RA lipossoma-hidrogel.

Artificial neural network modeling and optimization of ultrahigh pressure extraction of green tea polyphenols.

In this study, the ultrahigh pressure extraction of green tea polyphenols was modeled and optimized by a three-layer artificial neural network. A feed-forward neural network trained with an error back-propagation algorithm was used to evaluate the effects of pressure, liquid/solid ratio and ethanol concentration on the total phenolic content of green tea extracts. The neural network coupled with genetic algorithms was also used to optimize the conditions needed to obtain the highest yield of tea polyphenols. The obtained optimal architecture of artificial neural network model involved a feed-forward neural network with three input neurons, one hidden layer with eight neurons and one output layer including single neuron. The trained network gave the minimum value in the MSE of 0.03 and the maximum value in the R(2) of 0.9571, which implied a good agreement between the predicted value and the actual value, and confirmed a good generalization of the network. Based on the combination of neural network and genetic algorithms, the optimum extraction conditions for the highest yield of green tea polyphenols were determined as follows: 498.8 MPa for pressure, 20.8 mL/g for liquid/solid ratio and 53.6% for ethanol concentration. The total phenolic content of the actual measurement under the optimum predicated extraction conditions was 582.4 ± 0.63 mg/g DW, which was well matched with the predicted value (597.2mg/g DW). This suggests that the artificial neural network model described in this work is an efficient quantitative tool to predict the extraction efficiency of green tea polyphenols.