PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect

As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity.     

Cardiolipin-based respiratory complex activation in bacteria

Anionic lipids play a variety of key roles in membrane function, including functional and structural effects on respiratory complexes. However, little is known about the molecular basis of these lipid-protein interactions. In this study, NarGHI, an anaerobic respiratory complex of Escherichia coli, has been used to investigate the relations in between membrane-bound proteins with phospholipids. Activity of the NarGHI complex is enhanced by anionic phospholipids both in vivo and in vitro. The anionic cardiolipin tightly associates with the NarGHI complex and is the most effective phospholipid to restore functionality of a nearly inactive detergent-solubilized enzyme complex. A specific cardiolipin-binding site is identified on the basis of the available X-ray diffraction data and of site-directed mutagenesis experiment. One acyl chain of cardiolipin is in close proximity to the heme b(D) center and is responsible for structural adjustments of b(D) and of the adjacent quinol substrate binding site. Finally, cardiolipin binding tunes the interaction with the quinol substrate. Together, our results provide a molecular basis for the activation of a bacterial respiratory complex by cardiolipin.     

Direct visualization reveals dynamics of a transient intermediate during protein assembly

Interactions between proteins underlie numerous biological functions. Theoretical work suggests that protein interactions initiate with formation of transient intermediates that subsequently relax to specific, stable complexes. However, the nature and roles of these transient intermediates have remained elusive. Here, we characterized the global structure, dynamics, and stability of a transient, on-pathway intermediate during complex assembly between the Signal Recognition Particle (SRP) and its receptor. We show that this intermediate has overlapping but distinct interaction interfaces from that of the final complex, and it is stabilized by long-range electrostatic interactions. A wide distribution of conformations is explored by the intermediate; this distribution becomes more restricted in the final complex and is further regulated by the cargo of SRP. These results suggest a funnel-shaped energy landscape for protein interactions, and they provide a framework for understanding the role of transient intermediates in protein assembly and biological regulation.     

Iron‐Containing Poly(propylene imine) Dendromesogens with Photoactive Properties

Here, we report the first results of investigation the local structure and photoactive properties of iron‐containing dendromesogens based on decyloxybenzoate substituted poly(propylene imine) dendrimers of the first to fifth generations. Iron ions existing in a high‐spin state are coordinated in dendrimer ligands by two kinds of iron‐complexing sites with an octahedral and a tetrahedral symmetry. Octahedral (high‐symmetry) centers are located at the border of the dendrimeric core, while the tetrahedral centers with strong rhombic distortion of iron environment are distributed throughout all branching of the dendrimeric core. It has been found that all iron‐containing dendromesogens exhibit light‐harvesting and fluorescence properties.

     

Molecular and magnetic resonance imaging: The value of immunoliposomes

Molecular imaging has the potential to transform the field of diagnostic imaging through enabling far more detailed investigation and characterisation of disease processes than is currently possible. Magnetic resonance imaging (MRI) is capable of three-dimensional non-invasive imaging of opaque tissues at near cellular resolution. Among the imaging techniques available today, MRI has, perhaps, the greatest potential to exploit the possibilities that molecular imaging presents. Nanoparticles are the focus of intense research, due to a wide variety of potential applications in the biomedical, optical, and electronic fields. In this article we examine the progress made in the development of nanoparticles as targeted contrast agents for molecular magnetic resonance imaging. In particular, we will examine the potential of antibody-targeted liposomes (immunoliposomes) as vehicles for delivering MRI contrast agents to cellular biomarkers, thus enabling visualisation of structures and processes at the molecular level. We will address some of the challenges that must be faced by researchers in this field before the progress made in the laboratory can be translated into improved clinical diagnostics and therapeutics.     

Modulating pH-independent release from coated pellets: Effect of coating composition on solubilization processes and drug release

The aim of the study was to clarify the influences of three coating parameters on the drug release from chlorpheniramine maleate (CPM) pellets, coated with blends of poly(vinyl acetate) (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A central composite design was implemented to investigate the effect of the polymer blend ratio, the film coat thickness and the plasticizer concentration on the drug release. The solubilization inside the pellets was monitored by EPR spectroscopy. The blending ratio of both the polymers and the film thickness were found to have a major influence on the drug release and the solubilization speed, in contrast to the plasticizer concentration. A pH-independent release profile was adjustable via modulating the polymer blend ratio and the coating thickness. A mathematical model was developed, providing a good predictability of the release profile, based on the film coat composition. This model offers the possibility to achieve a defined drug-release profile by selective adaptation of the film coat composition, in view of process times, feasibility or polymer costs.     

Efficient high capacity technique to embed EPR information and to detect tampering in medical images

Abstract

Reversible data hiding (RDH) is one of the well-known and highly recommended method to enhance medical data security or electronic patient record (EPR), privacy and truthfulness. In clinical images, while hiding the data, care must be taken to maintain the confidentiality of the information that is to be hidden within the clinical images because the hidden information should not bring down the original quality of the image. Mostly, the investigations carried out for medical diagnosis are usually constructed on the basis of investigation systems used for diagnosis and are grounded on the images usually used for medical study. Magnetic resonance image (MRI), CR and CT, digital format images which are acquired are related to the patient’s data and information regarding their diagnosis study. In this presented approach, we introduce an RDH scheme that can also be combined with encryption and reversible watermarking techniques. Here, we use the data related to the patient diagnosis as the secret information to embed in medical images. Quality of the marked image after embedding the data is usually measured with metrics that are usually used in image processing such as PSNR and SSIM.     

Visualization of free radical reactions in an aqueous sample irradiated by 290 MeV carbon beam

The detection of free radical reactions in a gelatin sample irradiated by a heavy‐ion beam was tested using electron paramagnetic resonance (EPR) spectroscopic and MRI methods. Geometry and the amount of free radical generation in a sample are described. A reaction mixture containing glutathione and a nitroxyl radical, TEMPOL, was caked with gelatin, and then irradiated with a 290 MeV carbon beam. The amount of free radical generation in a solid sample was almost flat from the surface to the beam end, except for a small peak, the peak radioactivation profile, and then steeply decreased approaching the beam end. Total free radical reactions obtained with carbon‐beam irradiation were expected to be less than one‐third of X‐ray irradiation, when the same dose for a deeper target was considered. Both EPR and MRI are useful tools to visualize free radical generation in samples irradiated by a heavy‐ion beam. The EPR‐based method is more sensitive and quantitative than the MRI‐based method; however, the MRI method can achieve high spatial resolution. This study gives the rationale for a redox regulation trial using antioxidant drugs to reduce the side effects on normal tissues in carbon‐beam therapy. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Resolution‐recovery for EPR imaging of free radical molecules in mice

A method of post‐processing to enhance the image resolution of the distribution of free radical molecules obtained with continuous‐wave electron paramagnetic resonance (CW‐EPR) imaging is reported. The low spatial resolution of EPR imaging, which has created difficulties in biomedical applications, was overcome by the method of resolution‐recovery for EPR imaging. High spatial resolution images for the distribution of free radical molecules with a very short relaxation time were obtained with this method. The method's two‐step postprocessing consists of conventional deconvolution and filtered back‐projection and a process of iterative deconvolution. The resolution‐recovery method was demonstrated with three‐dimensional (3D) imaging of stable nitroxyl radicals in mouse head. In phantom experiments with a solution of triarylmethyl (TAM) radicals, the spatial resolution was improved by a factor of 7 with the resolution‐recovery method. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Improvements of cellular stress response on resveratrol in liposomes

Resveratrol (RSV) has proven potential in prophylaxis and treatment of various disorders mediated by free radicals and oxidative stress. RSV solubility, stability, and cytotoxicity must be regulated for satisfactory bioavailability. Here, RSV was loaded into liposomes, characterized by PCS and TEM and evaluated on HEK293 cell line by metabolic activity assay, electron paramagnetic resonance, and fluorescence microscopy.RSV at 10 μM induced changes in cell metabolic activity and significantly improved antioxidative capacity. At 100 μM it showed concentration-dependent cytotoxicity. Oligolamellar liposomes with mean diameter 84 nm, polydispersity index 0.2, and zeta potential −40 mV showed high entrapment of RSV and rapid cellular internalization. Cell stress caused by UV-B irradiation diminished cell metabolic activity by 50%. RSV loaded into them showed no cytotoxicity at 100 μM and stimulated cellular metabolic and antioxidant activity levels to eliminate the harmful effect of the stress. Localization of RSV within liposomal bilayer is crucial for stimulation of cell-defense system, prevention of RSV cytotoxicity, and its long-term stability. In summary, evidence of different metabolic activity using free RSV and LIP–RSV is presented indicating that liposome-mediated uptake of RSV is more effective for improvement of the cell-stress response.