Lipospheres and pro-nano lipospheres for delivery of poorly water soluble compounds

Lipospheres are a drug encapsulation system composed of water dispersible solid microparticles of particle size between 0.01 and 100 μm in diameter with a solid hydrophobic lipid core stabilized by a layer of phospholipid molecules embedded in their surface. The bioactive compound is dissolved or dispersed in the solid lipid matrix of the internal core. Since lipospheres were introduced in the beginning of the 1990s, they have been used for the delivery of multiple types of drugs by various routes of administration. Later, a self-assembling pro-nano lipospheres (PNL) encapsulation system was developed for oral drug delivery. Lipospheres have several advantages over other delivery systems, such as better physical stability, low cost of ingredients, ease of preparation and scale-up, high dispersibility in an aqueous medium, high entrapment of hydrophobic drugs, controlled particle size, and extended release of entrapped drug after administration, from a few hours to several days. This review article focuses on updated information on several aspects of lipospheres and PNL, including preparation techniques, physicochemical properties and in vitro evaluation methods. Additionally, it covers lipospheres and PNL utilization for oral, ocular, and parenteral delivery, with special attention to unique considerations and aspects for each route of administration.     

Bio-shielding <Emphasis Type="Italic">In Situ</Emphasis> Forming Gels (BSIFG) Loaded With Lipospheres for Depot Injection of Quetiapine Fumarate: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

Quetiapine fumarate (QF), an anti-schizophrenic drug, suffers from rapid elimination and poor bioavailability due to extensive first-pass effect. Intramuscularly (IM) injected lipospheres were designed to enhance the drug’s bioavailability and extend its release. A central composite design was applied to optimize the liposphere preparation by a melt dispersion technique using Compritol® 888 ATO or glyceryl tristearate as lipid component and polyvinyl alcohol as surfactant. Lipospheres were evaluated for their particle size, entrapment efficiency, and in vitro release. The optimized QF lipospheres were prepared using a Compritol® 888 ATO fraction of 18.88% in the drug/lipid mixture under a stirring rate of 3979 rpm. The optimized lipospheres were loaded into a thermoresponsive in situ forming gel (TRIFG) and a liquid crystalline in situ forming gel (LCIFG) to prevent in vivo degradation by lipases. The loaded gels were re-evaluated for their in vitro release and injectability. Bioavailability of QF from liposphere suspension and bio-shielding in situ gels loaded with QF lipospheres were assessed in rabbits compared to drug suspension. Results revealed that the AUC_0–72 obtained from the liposphere-loaded TRIFG was ～3-fold higher than that obtained from the aqueous drug suspension indicating the bio-shielding effect of Poloxamer® 407 gel to inhibit the biodegradation of the lipospheres prolonging the residence of the drug in the muscle for higher absorption. Our results propose that bio-shielding in situ Poloxamer® 407 gels loaded with lipospheres is promising for the development of IM depot injection of drugs having extensive first-pass metabolism and rapid elimination.     

Lipospheres as Carriers for Topical Delivery of Aceclofenac: Preparation,Characterization and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Evaluation

The purpose of this study was to prepare lipospheres containing aceclofenac intended for topical skin delivery with the aim of exploiting the favorable properties of this carrier system and developing a sustained release formula to overcome the side effects resulting from aceclofenac oral administration. Lipospheres were prepared using different lipid cores and phospholipid coats adopting melt and solvent techniques. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis, DSC, In vitro drug release and storage study. The anti-inflammatory effect of liposphere systems was assessed by the rat paw edema technique and compared to the marketed product. Results revealed that liposphere systems were able to entrap aceclofenac at very high levels (93.1%). The particle size of liposphere systems was well suited for topical drug delivery. DSC revealed the molecular dispersion of aceclofenac when incorporated in lipospheres. Both entrapment efficiency and release were affected by the technique of preparation, core and coat types, core to coat ratio and drug loading. Lipospheres were very stable after 3 months storage at 2–8°C manifested by low leakage rate (less than 7%) and no major changes in particle size. Finally, liposphere systems were found to possess superior anti-inflammatory activity compared to the marketed product in both lotion and paste consistencies. Liposphere systems proved to be a promising topical system for the delivery of aceclofenac as they possessed the ability to entrap the drug at very high levels and high stability, and to sustain the anti-inflammatory effect of the drug.     

In Situ Subangstrom‐Thick Organic Engineering Enables Mono‐scale,Ultrasmall ZnO Nanocrystals for a High Initial Coulombic Efficiency,Fully Reversible Conversion,and Cycle‐Stable Li‐Ion Storage

A solid electrolyte interphase (SEI)‐free surface and fully reversible conversion are simultaneously realized in the Li‐ion storage of a specially designed ZnO porous nanocomposite with in situ surfaces/interfaces organic encapsulation for the first time. The built‐in oxygen‐ and/or moisture‐isolating organic layer of subangstrom thickness not only avoids the SEI formation, but also guarantees monodisperse and ultrasmall dimensions of ZnO nanocrystals, which are crucial for the high initial Coulombic efficiency (ICE) and fully reversible conversion. Benefiting from the high ICE up to 91.4%, stable long‐term cyclibility (95% capacity retention at 1 A g^?1 after 1400 cycles), and no sacrificing Li‐ion storage capability (868 mAh g^?1 at 0.1 A g^?1), the ZnO nanocomposite demonstrates the highest initial Li‐ion utilization efficiency (ILUE, ≈85.4%) among previous transition metal oxide–based full cells.     

In Situ Generation of Few‐Layer Graphene Coatings on SnO2‐SiC Core‐Shell Nanoparticles for High‐Performance Lithium‐Ion Storage

A simple ball‐milling method is used to synthesize a tin oxide‐silicon carbide/few‐layer graphene core‐shell structure in which nanometer‐sized SnO₂ particles are uniformly dispersed on a supporting SiC core and encapsulated with few‐layer graphene coatings by in situ mechanical peeling. The SnO₂‐SiC/G nanocomposite material delivers a high reversible capacity of 810 mA h g^?1 and 83% capacity retention over 150 charge/discharge cycles between 1.5 and 0.01 V at a rate of 0.1 A g^?1. A high reversible capacity of 425 mA h g^?1 also can be obtained at a rate of 2 A g^?1. When discharged (Li extraction) to a higher potential at 3.0 V (vs. Li/Li⁺), the SnO₂‐SiC/G nanocomposite material delivers a reversible capacity of 1451 mA h g^?1 (based on the SnO₂ mass), which corresponds to 97% of the expected theoretical capacity (1494 mA h g^?1, 8.4 equivalent of lithium per SnO₂), and exhibits good cyclability. This result suggests that the core‐shell nanostructure can achieve a completely reversible transformation from Li_4.4Sn to SnO₂ during discharging (i.e., Li extraction by dealloying and a reversible conversion reaction, generating 8.4 electrons). This suggests that simple mechanical milling can be a powerful approach to improve the stability of high‐performance electrode materials involving structural conversion and transformation.     

Actinomycetes scale‐up for the production of the antibacterial,nocathiacin

An Amycolatopsis fastidiosa culture, which produces the nocathiacin class of antibacterial compounds, was scaled up to the 15,000 L working volume. Lower volume pilot fermentations (600, 900, and 1,500 L scale) were conducted to determine process feasibility at the 15,000 L scale. The effects of inoculum volume, impeller tip speed, volumetric gas flow rate, superficial gas velocity, backpressure, and sterilization heat stress were examined to determine optimal scale‐up operating conditions. Inoculum volume (6 vs. 2 vol %) and medium sterilization (R_o of 68 vs. 92 min^?1) had no effect on productivity or titer, and higher impeller tip speeds (2.1 vs. 2.9 m/s) had a slight effect (20% decrease). In contrast, higher backpressure, incorporating increased head pressure at the 15,000 L scale (1.2 vs. 0.7 kg/cm²) and low gas flow rates (0.25 vs. 0.8 vvm), appeared to be problematic (40–50% decrease). High off‐gas CO₂ levels were likely reasons for observed lower productivity. Consequently, air flow rate for this 25‐fold scale‐up (600–15,000 L) was controlled to match off‐gas CO₂ profiles of acceptable smaller scale batches to maintain levels below 0.5%. The 15,000 L‐scale fermentation achieved an expected nocathiacin I titer of 310 mg/L after 7 days. Other on‐line data (i.e., pH, oxygen uptake rate, and CO₂ evolution rate) and off‐line data (i.e., analog production, glucose utilization, ammonium production, and dry cell weight) at the 15,000 L scale also tracked similarly to the smaller scale, demonstrating successful fermentation scale‐up. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009     

A High‐Volumetric‐Capacity Cathode Based on Interconnected Close‐Packed N‐Doped Porous Carbon Nanospheres for Long‐Life Lithium–Sulfur Batteries

This study reports a Li–S battery cathode of high volumetric capacity enabled by novel micro‐ and mesostructuring. The cathode is based on monodisperse highly porous carbon nanospheres derived from a facile template‐ and surfactant‐free method. At the mesoscale, the nanospheres structure into interconnected close‐packed clusters of a few microns in extent, thus facilitating the fabrication of dense crack‐free high areal sulfur loading (5 mg cm^?2) cathodes with high electrical conductivity and low cathode impedance. A combination of the nitrogen doping (5 wt%), high porosity (2.3 cm³ g^?1), and surface area (2900 m² g^?1) at the microscale enables high sulfur immobilization and utilization. The cathode delivers among the best reported volumetric capacity to date, above typical Li‐ion areal capacity at 0.2 C over 200 cycles and low capacity fading of 0.1% per cycle at 0.5 C over 500 cycles. The compact cathode structure also ensures a low electrolyte requirement (6 µL mg^?1), which aids a low overall cell weight, and further, among the best gravimetric capacities published to date as well.     

Exploring Advanced Sandwiched Arrays by Vertical Graphene and N‐Doped Carbon for Enhanced Sodium Storage

Smart hybridization of active materials into tailored electrode structure is highly important for developing advanced electrochemical energy storage devices. With the help of sandwiched design, herein a powerful strategy is developed to fabricate three‐layer sandwiched composite core/shell arrays via combined hydrothermal and polymerization approaches. In such a unique architecture, wrinkled MoSe₂ nanosheets are sandwiched by vertical graphene (VG) core and N‐doped carbon (N‐C) shell forming sandwiched core/shell arrays. Interesting advantages including high electrical conductivity, strong mechanical stability, and large porosity are combined in the self‐supported VG/MoSe₂/N‐C sandwiched arrays. As a preliminary test, the sodium ion storage properties of VG/MoSe₂/N‐C sandwiched arrays are characterized and demonstrated with high capacity (540 mA h g^?1), enhanced high rate capability, and long‐term cycling stability (298 mA h g^?1 at 2.0 A g^?1 after 1000 cycles). The sandwiched core/shell structure plays positive roles in the enhancement of electrochemical performances due to dual conductive carbon networks, good volume accommodation, and highly porous structure with fast ion diffusion. The directional electrode design protocol provides a general method for synthesis of high‐performance ternary core/shell electrodes.     

Alkaline Polymer Membrane‐Based Ultrathin,Flexible, and High‐Performance Solid‐State Zn‐Air Battery

The increasing demand for portable and wearable electronics requires lightweight, thin, and highly flexible power sources, for example, flexible zinc‐air batteries (ZABs). The so‐far reported flexible ZAB devices mostly remain bulky, with a design consisting of two relatively thick substrates (e.g., carbon cloths and/or metal foams) and a gel electrolyte‐coated separator in between. Herein, an ultrathin (≈0.2 mm) solid‐state ZAB with high flexibility and performance is introduced by directly forming self‐standing active layers on each surface of an alkaline polymer membrane through an ink‐casting/hot‐pressing approach. A Fe/N‐doped 3D carbon with hierarchic pores and an interconnected network structure is used as cathode electrocatalyst, so that the backing gas‐diffusion layer (e.g., carbon cloth) can be abandoned. What is further, a microstructure‐modulating method to significantly increase the FeN₄ active sites for oxygen reduction reaction is developed, thus significantly boosting the performance of the ZAB. The assembled solid‐state ZAB manifests remarkable peak power density of 250 mW cm^?3 and high capacity of 150.4 mAh cm^?3 at 8.3 mA cm^?3, as well as excellent flexibility. The new design should provide valuable opportunity to the portable and wearable electronics.     

Plasticity in gas‐exchange physiology of mature Scots pine and European larch drive short‐ and long‐term adjustments to changes in water availability

Adjustment mechanisms of trees to changes in soil‐water availability over long periods are poorly understood, but crucial to improve estimates of forest development in a changing climate. We compared mature trees of Scots pine (Pinus sylvestris) and European larch (Larix decidua) growing along water‐permeable channels (irrigated) and under natural conditions (control) at three sites in inner‐Alpine dry valleys. At two sites, the irrigation had been stopped in the 1980s. We combined measurements of basal area increment (BAI), tree height and gas‐exchange physiology (Δ¹³C) for the period 1970–2009. At one site, the Δ¹³C of irrigated pine trees was higher than that of the control in all years, while at the other sites, it differed in pine and larch only in years with dry climatic conditions. During the first decade after the sudden change in water availability, the BAI and Δ¹³C of originally irrigated pine and larch trees decreased instantly, but subsequently reached higher levels than those of the control by 2009 (15 years afterwards). We found a high plasticity in the gas‐exchange physiology of pine and larch and site‐specific responses to changes in water availability. Our study highlights the ability of trees to adjust to new conditions, thus showing high resilience.     

Li+ Pre‐Insertion Leads to Formation of Solid Electrolyte Interface on TiO2 Nanotubes That Enables High‐Performance Anodes for Sodium Ion Batteries

Recently, sodium ion batteries (SIBs) have been widely investigated as one of the most promising candidates for replacing lithium ion batteries (LIBs). For SIBs or LIBs, designing a stable and uniform solid electrolyte interphase (SEI) at the electrode–electrolyte interface is the key factor to provide high capacity, long‐term cycling, and high‐rate performance. In this paper, it is described how a remarkably enhanced SEI layer can be obtained on TiO₂ nanotube (TiO₂ NTs) arrays that allows for a strongly improved performance of sodium battery systems. Key is that a Li⁺ pre‐insertion in TiO₂ NTs can condition the SEI for Na⁺ replacement. SIBs constructed with Li‐pre‐inserted NTs deliver an exceptional Na⁺ cycling stability (e.g., 99.9 ± 0.1% capacity retention during 250 cycles at a current rate of 50 mA g^?1) and an excellent rate capability (e.g., 132 mA h g^?1 at a current rate of 1 A g^?1). The key factor in this outstanding performance is that Li‐pre‐insertion into TiO₂ NTs leads not only to an enhanced electronic conductivity in the tubes, but also expands the anatase lattice for facilitated subsequent Na⁺ cycling.     

STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites

StAR‐related lipid transfer domain‐3 (STARD3) is a sterol‐binding protein that creates endoplasmic reticulum (ER)–endosome contact sites. How this protein, at the crossroad between sterol uptake and synthesis pathways, impacts the intracellular distribution of this lipid was ill‐defined. Here, by using in situ cholesterol labeling and quantification, we demonstrated that STARD3 induces cholesterol accumulation in endosomes at the expense of the plasma membrane. STARD3‐mediated cholesterol routing depends both on its lipid transfer activity and its ability to create ER–endosome contacts. Corroborating this, in vitro reconstitution assays indicated that STARD3 and its ER‐anchored partner, Vesicle‐associated membrane protein‐associated protein (VAP), assemble into a machine that allows a highly efficient transport of cholesterol within membrane contacts. Thus, STARD3 is a cholesterol transporter scaffolding ER–endosome contacts and modulating cellular cholesterol repartition by delivering cholesterol to endosomes.     

In Situ Generation of Artificial Solid‐Electrolyte Interphases on 3D Conducting Scaffolds for High‐Performance Lithium‐Metal Anodes

Rational structure design of the current collector along with further engineering of the solid‐electrolyte interphases (SEI) layer is one of the most promising strategies to achieve uniform Li deposition and inhibit uncontrolled growth of Li dendrites. Here, a Li₂S layer as an artificial SEI with high compositional uniformity and high lithium ion conductivity is in situ generated on the surface of the 3D porous Cu current collector to regulate homogeneous Li plating/stripping. Both simulations and experiments demonstrate that the Li₂S protective layer can passivate the porous Cu skeleton and balance the transport rate of lithium ions and electrons, thereby alleviating the agglomerated Li deposition at the top of the electrode or at the defect area of the SEI layer. As a result, the modified current collector exhibits long‐term cycling of 500 cycles at 1 mA cm^?2 and stable electrodeposition capabilities of 4 mAh cm^?2 at an ultrahigh current density of 4 mA cm^?2. Furthermore, full batteries (LiFePO₄ as cathode) paired with this designed 3D anode with only ≈200% extra lithium show superior stability and rate performance than the batteries paired with lithium foil (≈3000% extra lithium). These explorations provide new strategies for developing high‐performance Li metal anodes.     

Mesoporous TiO2‐Sn/C Core‐Shell Nanowire Arrays as High‐Performance 3D Anodes for Li‐Ion Batteries

Three‐dimensional mesoporous TiO₂‐Sn/C core‐shell nanowire arrays are prepared on Ti foil as anodes for lithium‐ion batteries. Sn formed by a reduction of SnO₂ is encapsulated into TiO₂ nanowires and the carbon layer is coated onto it. For additive‐free, self‐supported anodes in Li‐ion batteries, this unique core‐shell composite structure can effectively buffer the volume change, suppress cracking, and improve the conductivity of the electrode during the discharge‐charge process, thus resulting in superior rate capability and excellent long‐term cycling stability. Specifically, the TiO₂‐Sn/C nanowire arrays display rechargeable discharge capacities of 769, 663, 365, 193, and 90 mA h g^?1 at 0.1C, 0.5C, 2C 10C, and 30C, respectively (1C = 335 mA g^?1). Furthermore, the TiO₂‐Sn/C nanowire arrays exhibit a capacity retention rate of 84.8% with a discharge capacity of over 160 mA h g^?1, even after 100 cycles at a high current rate of 10C.     

Sandwich‐Type Microporous Carbon Nanosheets for Enhanced Supercapacitor Performance

Sandwich‐type microporous hybrid carbon nanosheets (MHCN) consisting of graphene and microporous carbon layers are fabricated using graphene oxides as shape‐directing agent and the in‐situ formed poly(benzoxazine‐co‐resol) as carbon precursor. The reaction and condensation can be readily completed within 45 min. The obtained MHCN has a high density of accessible micropores that reside in the porous carbon with controlled thickness (e.g., 17 nm), a high surface area of 1293 m² g^?1 and a narrow pore size distribution of ca. 0.8 nm. These features allow an easy access, a rapid diffusion and a high loading of charged ions, which outperform the diffusion rate in bulk carbon and are highly efficient for an increased double‐layer capacitance. Meanwhile, the uniform graphene percolating in the interconnected MHCN forms the bulk conductive networks and their electrical conductivity can be up to 120 S m^?1 at the graphene percolation threshold of 2.0 wt.%. The best‐practice two‐electrode test demonstrates that the MHCN show a gravimetric capacitance of high up to 103 F g^?1 and a good energy density of ca. 22.4 Wh kg^?1 at a high current density of 5 A g^?1. These advanced properties ensure the MHCN a great promise as an electrode material for supercapacitors.     

Building Lithiophilic Ion‐Conduction Highways on Garnet‐Type Solid‐State Li+ Conductors

The integration of highly conductive solid‐state electrolytes (SSEs) into solid‐state cells is still a challenge mainly due to the high impedance existing at the electrolyte/electrode interface. Although solid‐state garnet‐based batteries have been successfully assembled with the assistance of an intermediate layer between the garnet and the Li metal anode, the slow discharging/charging rates of the batteries inhibits practical applications, which require much higher power densities. Here, a crystalline sulfonated‐covalent organic framework (COF) thin layer is grown on the garnet surface via a simple solution process. It not only significantly improves the lithiophilicity of garnet electrolytes via the lithiation of the COF layer with molten Li, but also creates effective Li⁺ diffusion “highways” between the garnet and the Li metal anode. As a result, the interfacial impedance of symmetric solid‐state Li cells is significantly decreased and the cells can be operated at high current densities up to 3 mA cm^?2, which is difficult to achieve with current interfacial modification technologies for SSEs. The solid‐state Li‐ion batteries using LiFePO₄ cathodes, Li anodes, and COF‐modified garnet electrolytes thus exhibit a significantly improved rate capability.     

Free‐energy profiles for ions in the influenza M2‐TMD channel

M₂ transmembrane domain channel (M₂‐TMD) permeation properties are studied using molecular dynamics simulations of M₂‐TMD (1NYJ) embedded in a lipid bilayer (DMPC) with 1 mol/kg NaCl or KCl saline solution. This study allows examination of spontaneous cation and anion entry into the selectivity filter. Three titration states of the M₂‐TMD tetramer are modeled for which the four His³⁷ residues, forming the selectivity filter, are net uncharged, +2 charged, or +3 charged. M₂‐TMD structural properties from our simulations are compared with the properties of other models extracted from NMR and X‐ray studies. During 10 ns simulations, chloride ions occasionally occupy the positively‐charged selectivity filter region, and from umbrella sampling simulations, Cl^? has a lower free‐energy barrier in the selectivity‐filter region than either Na⁺ or NH, and NH has a lower free‐energy barrier than Na⁺. For Na⁺ and Cl^?, the free‐energy barriers are less than 5 kcal/mol, suggesting that the 1NYJ conformation would probably not be exquisitely proton selective. We also point out a rotameric configuration of Trp⁴¹ that could fully occlude the channel. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

A two‐phase partitioning airlift bioreactor for the treatment of BTEX contaminated gases

This investigation characterizes a novel 11 L airlift two‐phase partitioning bioreactor (TPPB) for the treatment of gases contaminated with a mixture of benzene, toluene, ethylbenzene, and o‐xylene (BTEX). The application of the TPPB technology in an airlift bioreactor configuration provides a novel technology that reduces energy intensity relative to traditional stirred tank TPPB configurations. The addition of a solid second phase of silicone rubber beads (10%, v/v) or of a liquid second phase of silicone oil (10%, v/v) resulted in enhanced performance of the airlift bioreactor relative to the single phase case, with 20% more BTEX being removed from the gas phase during an imposed transient loading. During a 4 h loading step change of three times the nominal loading (60 g m^?3 h^?1), overall removal efficiencies for the airlift TPPBs containing a liquid or solid phase remained above 75%, whereas the single phase airlift had an overall removal efficiency of 47.1%. The airlift TPPB containing a silicone rubber second phase was further characterized by testing performance during steady‐state operation over a range of loadings and inlet gas flow rates in the form of a 3² factorial experimental design. Optimal operating conditions that avoid oxygen limitations and that still have a slow enough gas flow rate for sufficient BTEX transfer from the gas phase to the working volume are identified. The novel solid–liquid airlift TPPB reduces energy inputs relative to stirred tank designs while being able to eliminate large amounts of BTEX during both steady‐state and fluctuating loading conditions. Biotechnol. Bioeng. 2009;103: 1077–1086. © 2009 Wiley Periodicals, Inc.     

A Stable Graphitic,Nanocarbon‐Encapsulated,Cobalt‐Rich Core–Shell Electrocatalyst as an Oxygen Electrode in a Water Electrolyzer

The oxygen electrode plays a vital role in the successful commercialization of renewable energy technologies, such as fuel cells and water electrolyzers. In this study, the Prussian blue analogue‐derived nitrogen‐doped nanocarbon (NC) layer‐trapped, cobalt‐rich, core–shell nanostructured electrocatalysts (core–shell Co@NC) are reported. The electrode exhibits an improved oxygen evolution activity and stability compared to that of the commercial noble electrodes. The core–shell Co@NC‐loaded nickel foam exhibits a lower overpotential of 330 mV than that of IrO₂ on nickel foam at 10 mA cm^?2 and has a durability of over 400 h. The commercial Pt/C cathode‐assisted, core–shell Co@NC–anode water electrolyzer delivers 10 mA cm^?2 at a cell voltage of 1.59 V, which is 70 mV lower than that of the IrO₂–anode water electrolyzer. Over the long‐term chronopotentiometry durability testing, the IrO₂–anode water electrolyzer shows a cell voltage loss of 230 mV (14%) at 95 h, but the loss of the core–shell Co@NC–anode electrolyzer is only 60 mV (4%) even after 350 h cell‐operation. The findings indicate that the Prussian blue analogue is a class of inorganic nanoporous materials that can be used to derive metal‐rich, core–shell electrocatalysts with enriched active centers.     

Biochemical composition of haemagglutinin‐based influenza virus‐like particle vaccine produced by transient expression in tobacco plants

Influenza virus‐like particles (VLPs) are noninfectious particles resembling the influenza virus representing a promising vaccine alternative to inactivated influenza virions as antigens. Medicago inc. has developed a plant‐based VLP manufacturing platform allowing the large‐scale production of GMP‐grade influenza VLPs. In this article, we report on the biochemical compositions of these plant‐based influenza candidate vaccines, more particularly the characterization of the N‐glycan profiles of the viral haemagglutinins H1 and H5 proteins as well as the tobacco‐derived lipid content and residual impurities. Mass spectrometry analyses showed that all N‐glycosylation sites of the extracellular domain of the recombinant haemagglutinins carry plant‐specific complex‐type N‐glycans having core α(1,3)‐fucose, core β(1,2)‐xylose epitopes and Lewis^a extensions. Previous phases I and II clinical studies have demonstrated that no hypersensibility nor induction of IgG or IgE directed against these glycans was observed. In addition, this article showed that the plant‐made influenza vaccines are highly pure VLPs preparations while detecting no protein contaminants coming either from Agrobacterium or from the enzymes used for the enzyme‐assisted extraction process. In contrast, VLPs contain few host cell proteins and glucosylceramides associated with plant lipid rafts. Identification of such raft markers, together with the type of host cell impurity identified, confirmed that the mechanism of VLP formation in planta is similar to the natural process of influenza virus assembly in mammals.