Durga P. Acharya

Metal-free and MRI visible theranostic lyotropic liquid crystal nitroxide-based nanoparticles.

The development of improved, low toxicity, clinically viable nanomaterials that provide MRI contrast have tremendous potential to form the basis of translatable theranostic agents. Herein we describe a class of MRI visible materials based on lyotropic liquid crystal nanoparticles loaded with a paramagnetic nitroxide lipid. These readily synthesized nanoparticles achieved enhanced proton-relaxivities on the order of clinically used gadolinium complexes such as Omniscan™ without the use of heavy metal coordination complexes. Their low toxicity, high water solubility and colloidal stability in buffer resulted in them being well tolerated in vitro and in vivo. The nanoparticles were initially screened in vitro for cytotoxicity and subsequently a defined concentration range was tested in rats to determine the maximum tolerated dose. Pharmacokinetic profiles of the candidate nanoparticles were established in vivo on IV administration to rats. The lyotropic liquid crystal nanoparticles were proven to be effective liver MRI contrast agents. We have demonstrated the effective in vivo performance of a T1 enhancing, biocompatible, colloidally stable, amphiphilic MRI contrast agent that does not contain a metal.

Bicontinuous cubic phase nanoparticle lipid chemistry affects toxicity in cultured cells

Gaining an increased understanding of the toxicity of new lipid nanoparticle formulations such as the class of cubic and hexagonal phase forming nanomaterials called cubosomes™ and hexosomes™ is crucial for their development as therapeutic agents. Surprisingly, the literature on the in vitro and in vivo toxicity of cubic and hexagonal phase forming lipid nanoparticles is negligible, despite a rapidly growing number of publications on their potential use in various therapeutic applications. In this work we have developed methods to study the in vitro cytotoxicity of two chemically distinct cubic phase nanoparticle dispersions using the lipids glycerol monooleate and phytantriol respectively. We have found that the toxicity of phytantriol cubosomes is considerably greater than that of glycerol monooleate cubosomes. The increased toxicity of phytantriol appears to result from its greater ability to disrupt the cellular membrane (haemolytic activity) and oxidative stress. This finding has significant impact and can provide useful guidelines for those conducting further research on the use of cubic phase forming lipids for therapeutic and diagnostic applications both in vitro and in vivo.

Binding of resveratrol with sodium caseinate in aqueous solutions

The interaction between resveratrol (Res) and sodium caseinate (Na-Cas) has been studied by measuring fluorescence quenching of the protein by resveratrol. Quenching constants were determined using Stern-Volmer equation, which suggests that both dynamic and static quenching occur between Na-Cas and Res. Binding constants for the complexation between Na-Cas and Res were determined at different temperatures. The large binding constants (3.7-5.1×10(5)M(-1)) suggest that Res has strong affinity for Na-Cas. This affinity decreases as the temperature is raised from 25 to 37°C. The binding involves both hydrogen bonding and hydrophobic interaction, as suggested by negative enthalpy change and positive entropy change for the binding reaction. The present study indicates that Na-Cas, a common food protein, may be used as a carrier of Res, a bioactive polyphenol which is insoluble in both water and oils.

Nitroxide-loaded hexosomes provide MRI contrast in vivo

The purpose of this work was to synthesize and screen, for their effectiveness to act as T1-enhancing magnetic resonance imaging (MRI) contrast agents, a small library of nitroxide lipids incorporated into cubic-phase lipid nanoparticles (cubosomes). The most effective nitroxide lipid was then formulated into lower-toxicity lipid nanoparticles (hexosomes), and effective MR contrast was observed in the aorta and spleen of live rats in vivo. This new class of lower-toxicity lipid nanoparticles allowed for higher relaxivities on the order of those of clinically used gadolinium complexes. The new hexosome formulation presented herein was significantly lower in toxicity and higher in relaxivity than cubosome formulations previously reported by us.

Unusual Sydney dust storm and its mineralogical and organic characteristics

Environmental context In 2009, at the end of the longest drought period ever recorded in Australia, a major dust storm blanketed the cities of Sydney and Brisbane for more than 24u2009h. The source of the dust was inner New South Wales and South Australia, where large scale open-cut mining occurs together with agricultural practices. We report results of extensive mineralogical and chemical analyses of the dust, and discuss their significance in terms of the dust origins and potential human health risks. Abstract In a 24-h period from 23 to 24 September 2009, a dust storm passed over Sydney, Australia that produced a red sky and reduced the visibility to a few metres. It was Sydney’s worst dust storm since 1942. During this period, the PM10 (particles measuring 10u2009μm or less) value jumped from 50 to 11u2009800u2009µgu2009m–3. The dust storm was sampled and its mineralogical and organic contents were analysed. Four major particle sizes (0.6, 4.5, 9.3 and 20u2009µm) were observed in the dust. A multimodal particle distribution indicated a long range of dust transport. Mineralogical analysis showed that the particles were mainly composed of crustal elemental oxides of Al and Si. The ratio of Al/Si was 0.39 and the organic content was 10.6u2009%, which was found to be enriched with humic-type substances. The high Al/Si ratio (>0.3) indicated that the dust originated from desert land whereas the high organic content indicated that the particles were also derived from eroded agricultural land. A fluorescence spectroscopic study on the organic matter at excitation and emission wavelengths of 245–265 and 330–350u2009nm indicated that biohazardous substances were unlikely to be present in the dust.

Cubic mesophase nanoparticles doped with superparamagnetic iron oxide nanoparticles: A new class of MRI contrast agent

The ability of superparamagnetic iron oxide nanoparticles (SPIONs) to shorten the effective transverse relaxation time (T2) during magnetic resonance imaging (MRI) makes them excellent contrast agents in diagnostic applications. Here we describe a new class of hybrid MRI contrast agent using dispersions of lyotropic bicontinuous cubic phase nanoparticles doped with SPIONs. Hybrid mesophase nanoparticles (HMNs) combining the cubic order of a lyotropic lipid system and SPIONs were successfully prepared and characterized. Highly monodisperse 8 nm spherical SPIONs coated with oleic acid were dispersed in the bulk cubic phase forming lipid matrix of phytantriol nanoparticles 180 nm in size. Transverse relaxivity (r2) measurements show that enhancement of the T2 relaxation time of the HMNs is proportional to the loading of SPIONs in the mesophase nanoparticles. Excellent contrast enhancement in T2 weighted images in the kidney and liver of live rats was observed after intravenous injection of the hybrid mesophase nanoparticles. Results indicate that the HMNs are rapidly transported to the renal system making them useful for contrast enhancement of renal and hepatic systems.