Extracellular vesicles (EVs) are emerging as novel theranostic tools. Limitations related to clinical uses are leading to a new research area on design and manufacture of artificial EVs. Several ...strategies have been reported in order to produce artificial EVs, but there has not yet been a clear criterion by which to differentiate these novel biomaterials. In this paper, we suggest for the first time a systematic classification of the terms used to build up the artificial EV landscape, based on the preparation method. This could be useful to guide the derivation to clinical trial routes and to clarify the literature. According to our classification, we have reviewed the main strategies reported to date for their preparation, including key points such as: cargo loading, surface targeting strategies, purification steps, generation of membrane fragments for the construction of biomimetic materials, preparation of synthetic membranes inspired in EV composition and subsequent surface decoration.
In this study, nanovesicles such as transfersomes, niosomes, and liposomes prepared by an ethanol injection method (EIM) (EIM) and formulated with soybean lecithin, Tween 80, Span 60, and ...cholesterol, are used to improve the bioavailability of taxifolin, a natural antioxidant with beneficial properties for health and food preservation. Morphology, stability, and the in‐vitro release of the optimal formulations are fully examined. The obtained results indicate that taxifolin‐loaded nanovesicles present sizes ranging between 98 and 215 nm along with a narrow size distribution (polydispersity index less than 0.250). The zeta potential of nanovesicles is negative and in the range of −20.40 to −32.20 mV. The optimal formulations with the maximum encapsulation efficiency (72–75%) are the transfersomes formulated with lecithin and Tween 80 in the presence and absence of cholesterol. Additionally, in vitro release behavior of nanovesicles shows low taxifolin released (3.68–10.13%) at intestinal conditions, whereas more than 90% of taxifolin is released in gastrointestinal conditions. The compatibility between taxifolin and nanovesicles components is confirmed by FTIR. Transmission electron microscopy demonstrates spherical shaped particles around 200 nm. Backscattering profiles variations show the potential application of taxifolin nanovesicles for producing fortified apple juice with excellent physical stability.
Practical Applications: Taxifolin is a flavanonol, which fulfills a particular task in preserving stable functions of the circulatory system owing to its special antioxidant ability and biological activity. Nevertheless, its low bioavailability is a salient drawback for biomedical and food applications. Thus, the current study is conducted to encapsulate taxifolin in nanovesicles (such as liposome, niosome, transfersome) by EIM to improve its bioavailability. Nanocarriers with relatively decent physical stability and high encapsulation efficiency can be brought about through Tween 80, soybean lecithin, and in the presence and absence of cholesterol as stabilizer which ensures the successful delivery of taxifolin to food formats such as beverages.
Taxifolin‐loaded nanovesicles (liposomes, niosomes, and transfersomes) are synthesized by an ethanol injection method (EIM). Optimized formulations (transfersomes) are characterized and used for fortification of apple juice.
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•Vesicle size depend on the composition of the hydrating solution.•PEG-400 aqueous-based solution led the formation of larger vesicles than glycerol and aqueous based ...media.•Encapsulation efficiency (EE) increased when poly-ol based solution were used, probably because the bigger vesicle size.•Vesicle size was affected by the molecular weight of the compounds incorporated.•The composition of the hydrating solution might enhance the EE especially in particular cases.
Encapsulation into nanocarriers, such as niosomes, is a promising way to protect them from degradation, and allow controll and target delivery of bioactive compounds. For biotechnological applications, a tight control of particle size with acceptable encapsulation efficiencies (EE) is a technological challenge, especially for hydrophilic compounds due to its capability to diffuse across biological barriers. Niosomes formulated with mixture of surfactants represent promising nanocarriers due to the advantages of non-ionic surfactants, such as low cost, versatility and enhanced physico-chemical properties. In this work, the effect of both, composition of the hydrating solution and molecular weight of the loaded compound, on the particle size and EE of niosomes prepared by using the thin film hydration method was studied. Particularly, mili-Q water, glycerol solution and PEG-400 solution were tested for niosomes formulated with Span®80-Tween®80 with/without dodecanol as membrane stabilizer. It was found that particle size highly depends on hydration media composition and an interaction with compound MW could exist. Larger vesicles results in an increase in EE, which could be purely related with physical aspects such as vesicle loading volume capacity. The effect of hydration solution composition could be related with their ability to change the bilayer packing and physical properties, as observed by differential scanning calorimetry. Finally, it was possible to compare the suitability of dialysis and gel filtration as purification methods, demonstrating that gel filtration is not an adequate purification method when viscous solutions are used, since they could affect the particle vesicles retention and hence EE measurements would be misrepresentative.
Fully Artificial Exosomes: Towards New Theranostic Biomaterials García-Manrique, Pablo; Gutiérrez, Gemma; Blanco-López, Maria Carmen
Trends in biotechnology (Regular ed.),
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
36, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Bionanotechnology routes have been recently developed to produce fully artificial exosomes: biomimetic particles designed to overcome certain limitations in extracellular vesicle (EV) biology and ...applications. These particles could soon become true therapeutic biomaterials. Here, we outline their current preparation techniques, their explored and future possibilities, and their present limits.
Selection of competent recipients before embryo transfer (ET) is indispensable for improving pregnancy and birth rates in cattle. However, pregnancy prediction can fail when the competence of the ...embryo is ignored. We hypothesized that the pregnancy potential of biomarkers could improve with information on embryonic competence. In vitro-produced embryos cultured singly for 24 h (from d 6 to 7) were transferred to d 7 synchronized recipients as fresh or after freezing and thawing. Recipient blood was collected on d 0 (estrus; n = 108) and d 7 (4–6 h before ET; n = 107) and plasma was analyzed by nuclear magnetic resonance (1H+NMR). Spent embryo culture medium (CM) was collected and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry in a subset of n = 70 samples. Concentrations of metabolites quantified in plasma (n = 35) were statistically analyzed as a function of pregnancy diagnosed on d 40, d 62 and birth. Univariate analysis with plasma metabolites consisted of a block study with controllable fixed factors (i.e., embryo cryopreservation, recipient breed, and day of blood collection; Wilcoxon test and t-test). Metabolite concentrations in recipients and embryos were independently analyzed by iterations that reclassified embryos or recipients using the support vector machine. Iterations identified some competent embryos, but mostly competent recipients that had a pregnancy incompetent partner embryo. Misclassified recipients that could be classified as competent were reanalyzed in a new iteration to improve the predictive model. After subsequent iterations, the predictive potential of recipient biomarkers was recalculated. On d 0, creatine, acetone and l-phenylalanine were the most relevant biomarkers at d 40, d 62, and birth, and on d 7, l-glutamine, l-lysine, and ornithine. Creatine was the most representative biomarker within blocks (n = 20), with a uniform distribution over pregnancy endpoints and type of embryos. Biomarkers showed higher abundance on d 7 than d 0, were more predictive for d 40 and d 62 than at birth, and the pregnancy predictive ability was lower with frozen-thawed (F-T) embryos. Six metabolic pathways differed between d 40 pregnant recipients for fresh and F-T embryos. Within F-T embryos, more recipients were misclassified, probably due to pregnancy losses, but were accurately identified when combined with embryonic metabolite signals. After recalculation, 12 biomarkers increased receiver operator characteristic-area under the curve (>0.65) at birth, highlighting creatine (receiver operator characteristic-area under the curve = 0.851), and 5 new biomarkers were identified. Combining metabolic information of recipient and embryos improves the confidence and accuracy of single biomarkers.
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•A rapid and low-cost fabrication of flow reactors is presented.•The manufacturing procedure can be completed within one day, at the average material cost of £5.•Silver nanospheres ...and liposomes were synthesized using the 3D printed mould casting reactor.•Operation at total flow rates up to 20 ml/min was demonstrated.
The translation of continuous-flow microreactor technology to the industrial environment has been limited by cost and complexity of the fabrication procedures and the requirement for specialised infrastructure. In the present study, we have developed a significantly more cost-effective and easy-to-perform fabrication method for the generation of optically transparent, continuous-flow reactors. The method combines 3D printing of master moulds with sealing of the PDMS channels’ replica using a pressure-sensitive adhesive tape. Morphological characterisation of the 3D printed moulds was performed and reactors were fabricated with an approximately square-shaped cross-section of 1 mm2. Notably, they were tested for operation over a wide range of volumetric flow rates, up to 20 ml/min. Moreover, the fabrication time (i.e., from design to the finished product) was <1 day, at an average material cost of ∼£5. The flow reactors have been applied to the production of both inorganic nanoparticles (silver nanospheres) and organic vesicular systems (liposomes), and their performance compared with reactors produced using more laborious fabrication methods. Numerical simulations were performed to characterise the transport of fluids and chemical species within the devices. The developed fabrication method is suitable for scaled-up fabrication of continuous-flow reactors, with potential for application in biotechnology and nanomedicine.
The aim of this work was to prepare size-tuned nanovesicles using a modified ethanol injection method (EIM) by applying factorial experimental design. Stable size-tuned nanovesicles (liposomes and ...niosomes) with controlled sizes and high EE values for hydrophobic compounds (Sudan Red 7B and vitamin D3) were achieved. Equations that were able to predict the mean particle sizes, in the ranges of 55–156 nm for liposomes and 224–362 nm for niosomes with PDI values between 0.032 and 0.378, were obtained. These customized soft nanoparticles could be suitable in food, cosmetic, pharmaceutical, or medical applications, such as diagnosis or therapy.
•The CRMP created in 1986 was repealed in 2008, but its influence is present during the period studied.•ICZM lost importance between 2007 and 2017 in political agenda of Ecuador.•Absence specific ...regulations, institutions, coordination and resources explain the results of coastal management instrument.
The disaster caused by shrimp acuaculture in the mangrove forests of Ecuador was the driving force for internationally approved state action. For more than two decades Ecuador had been implementing a program of management of coastal resources (1986–2008). Furthermore, political changes in Ecuador between 2007 and 2017 also affected coastal management. These changes have been observed by analysing five key aspects related to ICZM: politics, strategies, regulation, institutions and instruments.
The results obtained indicate that the management of marine areas and resources were not well situated within the political agenda. Additionally the model employed for coastal management over the past decade was not the result of a specific policy of ICZM. On the contrary, the coast was governed by more general unconnected policies, namely environmental, spatial planning and social and economic policies.
Additionally Ecuador does not currently have the primary regulations in place to facilitate ICZM. Part of the previous regulation related to coastal management was repealed, meaning that the most relevant instruments of ICZM are struggling to move forward due to weak institutional capacity. It follows from the above that the coastal management model is at best confusing; implementation is slow and it returns poor results.
With direct participation of coastal resource users and a leading role being played by local public administration, interesting efforts can be observed in relation to guiding coastal management in protected coastal zones.
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•Monodispersed controlled size niosomes production by Microfluidics (MF) was studied.•Tween® 80 and Span® 80 were used in presence and absence of Dodecanol.•Results were compared to ...Thin Film Hydration (TFH) and Ethanol Injection (EI) methods.•MF showed an accurate control of the final size of the niosomes produced.•MF were smaller and more homogeneous to those achieved by TFH and similar to IE.
The extended use of niosomes in food, cosmetic and pharmaceutical industries demands novel preparation processes which could enhance nanovesicles production with controlled size and size distribution. Microfluidics (MF) are a novel promising set of preparation methods for this purpose. Studies comparing methods for niosome preparation are still scarce.
In this work, niosomes using MF were produced and the effect of membrane compounds concentration and the relation between organic and aqueous ratio (flow rate ratio, FRR) on the resulting mean size and size distribution were studied. Two different cholesterol free formulations were tested using Tween® 80 and Span® 80 in presence and absence of 1-dodecanol as membrane stabilizer. The effect of FRR showed to be the key parameter in niosomes production, being more critical than membrane compounds concentration and the vesicle membrane composition.
Additionally, the same formulations were also produced by two conventional methods, thin film hydration (TFH) and ethanol injection (EI), and results were compared. The size of the niosomes obtained by MF was smaller and more homogeneous than those achieved by TFH and similar to EI. Therefore, MF is confirmed as a novel technology that can facilitate the development and optimization of new nanodelivery systems with controlled size and polydispersity, two essential parameters for successful biotechnological applications.
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•Key parameters involved in a microfluidic reactor were investigated.•Temperature must be taken into consideration when formulating niosomes with surfactants with high Tm.•Ratio ...between aqueous and solvent streams has been the main parameter on mixing efficiency.
The new roles of vesicular systems in advanced biomedical, analytical and food science applications demand novel preparation processes designed to reach the new standards. Particle size and monodispersity have become essential properties to control. In this work, key parameters, involved in a microfluidic reactor with hydrodynamic flow focusing, were investigated in order to quantify their effects on niosomes morphology. Particular attention was given to temperature, which is both a requirement to handle non-ionic surfactants with phase transition temperature above RT, and a tailoring variable for size and monodispersity control. With this aim, niosomes with two different sorbitan esters and cholesterol as stabilizer were formulated. High resolution and conventional 3D-printing technologies were employed for the fabrication of microfluidic reactor and thermostatic systems, since this additive technology has been essential for microfluidics development in terms of cost-effective and rapid prototyping. A customised device to control temperature and facilitate visualization of the process was developed, which can be easily coupled with commercial inverted microscopes. The results demonstrated the capability of microfluidic production of niosomes within the full range of non-ionic surfactants and membrane stabilizers.
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