Recent advances in nanoneurology for drug delivery to the brain

The drug development for neurodegenerative disorders are the major challenge to the science in 21st century. Many FDA approved drugs currently available in the market have limitations in crossing the blood brain barrier (BBB) owing to its complicated vasculature posed by the presence of specialized cells. Nanotechnology is an emerging interdisciplinary area, which have many applications including drug delivery. Nanocarrier drug delivery involves targeting drugs enclosed in a particular polymer and/or amphiphilic lipids. Controlled release, nanoplatform availability for combinatorial therapy and tissue specific targeting by using advanced technologies such as molecular Trojan horse (MTH) technology are the promises of nanotechnology. Different problems are associated with drug delivery
across the BBB. Some are mostly related to the structure of brain microvasculature system while the others are related to the nanomaterial
structure. Different strategies, such as using polymeric/solid lipid nanoparticles and surface modification of nanomaterial with surfactants
like polysorbates have been conducted to solve these limitations. Also, nanodrug formulations with double coatings have been designed for oral delivery of drugs to overcome reticulo-endothelial system and to improve their BBB permeability. It seems that the best choice of strategy and material could be achieved with regard to the physical and chemical structure of the drugs. The present review discusses the potential applications of nanotechnology for drug delivery across the BBB.

Tristearin bilayers: structure of the aqueous interface and stability in the presence of surfactants

We report results of atomistic molecular dynamics simulations of an industrially-relevant, exemplar triacylglycerol (TAG), namely tristearin (TS), under aqueous conditions, at different temperatures and in the presence of an anionic surfactant, sodium dodecylbenzene sulphonate (SDBS). We predict the TS bilayers to be stable and in a gel phase at temperatures of 350 K and below. At 370 K the lipid bilayer was able to melt, but does not feature a stable liquid-crystalline phase bilayer at this elevated temperature. We also predict the structural characteristics of TS bilayers in the presence of SDBS molecules under aqueous conditions, where surfactant molecules are found to spontaneously insert into the TS bilayers. We model TS bilayers containing different amounts of SDBS, with the presence of SDBS imparting only a moderate effect on the structure of the system. Our study represents the first step in applying atomistic molecular dynamics simulations to the investigation of TAG-aqueous interfaces. Our results suggest that the CHARMM36 force-field appears suitable for the simulation of such systems, although the phase behaviour of the system may be shifted to lower temperatures than is the case for the actual system. Our findings provide a foundation for further simulation studies of the TS-aqueous interface.

Recent developments in mechanochemical nanoparticle synthesis

The results of recent investigations of the mechanochemical synthesis of CaC0₃, Cr₂0₃ and Nb₂0₅ nanopowders are reported. With all three materials studied, it is shown that the volume fraction of the matrix phase is crucial to the formation of separate, unagglomerated particles. With Cr₂0₃ and Nb₂0₅, amorphous particles were formed by mechanochemical reaction and low temperature heat treatment was required for crystallization. It is shown that, as a 'bottom up' process, mechanochemical processing enables the building up nanoparticles through solid-state chemical reaction in a microscopically uniform environment, leading to the formation of nanoparticles with narrow size distributions.

Nanoparticle enhanced conductivity in organic ionic plastic crystals : space charge versus strain induced defect mechanism

High conductivity in solid-state electrolytes is a critical requirement for many advanced energy and other electrochemical applications. Plastic crystalline materials have shown promise in this regard, and the inclusion of nanosized inorganic particles in both amorphous and crystalline materials has indicated order of magnitude enhancements in ion transport induced by space charge or other defect enhancement. In this paper we present conductivity enhancements in the plastic crystal N,N‘-ethylmethylpyrrolidinium bis(trifluoromethanesulfonyl)amide ([C₂mpyr][NTf₂]) induced by nanosized SiO₂ particles. The addition of the nanoparticles dramatically increases plasticity and ion mobility. Positron annihilation lifetime spectroscopy (PALS) measurements indicate an increase in mean defect size and defect concentration as a result of nanoparticle inclusion. The scaling of the conductivity with size suggests that a “trivial space charge” effect is operable, although a strain induced enhancement of defects (in particular extended defects) is also likely given the observed increase in plasticity.

Surprising effect of nanoparticle inclusion on ion conductivity in a lithium doped organic ionic plastic crystal

Doping lithium bis(trifluoromethanesulfonyl)amide (Li[NTf₂]) into the N-ethyl,N′-methylpyrrolidinium bis(trifluoromethanesulfonyl)amide ([C₂mpyr][NTf₂]) plastic crystal material has previously indicated order of magnitude enhancements in ion transport and conductivity over pure [C₂mpyr][NTf₂]. Recently, conductivity enhancements in this ionic plastic crystal induced by SiO₂ nanoparticles have also been reported. In this work the inclusion of SiO₂ nanoparticles in Li ion doped [C₂mpyr][NTf₂] has been investigated over a wide temperature range by differential scanning calorimetry (DSC), impedance spectroscopy, positron annihilation lifetime spectroscopy (PALS), Raman spectroscopy, NMR spectroscopy and scanning electron microscopy (SEM). Solid state ¹H NMR indicates that the addition of the nanoparticles increases the mobility of the [C₂mpyr] cation and positron lifetime spectroscopy (PALS) measurements indicate an increase in mean defect size and defect concentration as a result of nanoparticle inclusion, especially with 10 wt% SiO₂. Thus, the substantial drop in ion conductivity observed for this doped nanocomposite material was surprising. This decrease is most likely due to the decrease in mobility of the [NTf₂] anion, possibly by its adsorption at the SiO₂/grain boundary interface and concomitant decrease in mobility of the Li ion.

Lipid merging, protrusion and vesicle release triggered by shrinking/swelling of poly(N-isopropylacrylamide) microgel particles

Cell membrane changes its morphology during many physiological processes with the assistance of a solid support, such as the cytoskeleton, under an environmental stimulus. Here, a novel type of stimuli-responsive lipogel was fabricated, mimicking the changes of cell membrane. The lipogel was prepared from poly(N-isopropylacrylamide) (pNIPAM) microgel particle and phospholipid by a solvent-exchange method. The temperature dependent volume phase transition of pNIPAM triggers reversible transformation of the lipogel between a lipid vesicle-coated sun-like structure and a contracted hybrid sphere, through lipid merging and protrusion processes, respectively. By contrast, the salt induced pNIPAM phase transition leads to an irreversible vesicle release behaviour. The lipogel creates a unique platform for studying cell membrane behaviour and provides promising candidates in drug delivery and controlled release applications. © 2014 Elsevier B.V. All rights reserved.

Modulated deformation of lipid membrane to vesicles and tubes due to reduction of graphene oxide substrate under laser irradiation

Biomembrane transformations are closely related to many biological processes including endo/exocytosis and the cellular response to the local physical environment. In this work, we investigated the transformation between lipid membranes and lipid vesicles/tubes modulated by the solid substrate of graphene oxide (GO) aggregates under laser irradiation. We firstly fabricate a novel type of lipid@GO composite consisting of micrometer-sized GO aggregates surrounded by lamellar lipid membranes. Upon laser irradiation, lipid protrusion occurs and leads to the formation of vesicles adsorbed on the GO aggregate surface, with an average size as 0.43 times of the radius of GO aggregate. Both the location and the dynamic formation process of vesicles can be modulated. The arising of vesicles prefers to occur at edges of the GO planes rather than on surface of individual GO sheets within the GO aggregate. Furthermore, at a reduced laser power density, the lipid protrusion mainly grows to tubes instead of vesicles. Such transformations from lipid membrane to vesicles and tubes is ascribed to the reduction of GO to reduced-GO (rGO) under laser irradiation, probably along with the release of gases leading to the deformation of lipid membrane surrounding the GO surface.

A simple method for measuring carbon-13 fatty acid enrichment in the major lipid classes of microalgae using GC-MS

A simple method for tracing carbon fixation and lipid synthesis in microalgae was developed using a combination of solid-phase extraction (SPE) and negative ion chemical ionisation gas chromatography mass spectrometry (NCI-GC-MS). NCI-GC-MS is an extremely sensitive technique that can produce an unfragmented molecular ion making this technique particularly useful for stable isotope enrichment studies. Derivatisation of fatty acids using pentafluorobenzyl bromide (PFBBr) allows the coupling of the high separation efficiency of GC and the measurement of unfragmented molecular ions for each of the fatty acids by single quadrupole MS. The key is that isotope spectra can be measured without interference from co-eluting fatty acids or other molecules. Pre-fractionation of lipid extracts by SPE allows the measurement of13C isotope incorporation into the three main lipid classes (phospholipids, glycolipids, neutral lipids) in microalgae thus allowing the study of complex lipid biochemistry using relatively straightforward analytical technology. The high selectivity of GC is necessary as it allows the collection of mass spectra for individual fatty acids, including cis/trans isomers, of the PFB-derivatised fatty acids. The combination of solid-phase extraction and GC-MS enables the accurate determination of13C incorporation into each lipid pool. Three solvent extraction protocols that are commonly used in lipidomics were also evaluated and are described here with regard to extraction efficiencies for lipid analysis in microalgae.