Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.

Recent advances with liposomes as pharmaceutical carriers.

Liposomal drug delivery systems: from concept to clinical applications.

The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review

A level set method for structural topology optimization

Non-phagocytic eukaryotic cells can internalize particles <1 microm in size, encompassing pathogens, liposomes for drug delivery or lipoplexes applied in gene delivery. In the present study, we have investigated the effect of particle size on the pathway of entry and subsequent intracellular fate in non-phagocytic B16 cells, using a range of fluorescent latex beads of defined sizes (50-1000 nm). Our data reveal that particles as large as 500 nm were internalized by cells via an energy-dependent process. With an increase in size (50-500 nm), cholesterol depletion increased the efficiency of inhibition of uptake. The processing of the smaller particles was significantly perturbed upon microtubule disruption, while displaying a negligible effect on that of the 500 nm beads. Inhibitor and co-localization studies revealed that the mechanism by which the beads were internalized, and their subsequent intracellular routing, was strongly dependent on particle size. Internalization of microspheres with a diameter <200 nm involved clathrin-coated pits. With increasing size, a shift to a mechanism that relied on caveolae-mediated internalization became apparent, which became the predominant pathway of entry for particles of 500 nm in size. At these conditions, delivery to the lysosomes was no longer apparent. The data indicate that the size itself of (ligand-devoid) particles can determine the pathway of entry. The clathrin-mediated pathway of endocytosis shows an upper size limit for internalization of approx. 200 nm, and kinetic parameters may determine the almost exclusive internalization of such particles along this pathway rather than via caveolae.

Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis

Considerable progress has been achieved in understanding the mechanism of entry of enveloped viruses into host cells during the last few years. Viruses have long been known to be capabable of transporting their genome and accessory proteins into the cytosol of the host cell, thus causing infections of variable severity. It is clear that the medical consequences of viral diseases remain an important reason to study the cellular entry of viruses, particularly since a knowledge of the molecular details underlying this event may help to develop new antiviral strategies. Apart from their importance as pathogens, viruses, particularly enveloped viruses, have proven to be an excellent tool for studying protein synthesis, processing and sorted transport, thus greatly contributing to our current knowledge of the complex pathways of intracellular traffic. To infect a host cell, enveloped viruses have evolved a mechanism which involves membrane fusion. Although the molecular details of this process remain unclear, it has been well established that specific virally encoded membrane proteins are responsible for triggering the fusion reaction. Because of the simplicity of the viral membrane protein composition of most enveloped viruses, viral systems provide a valuable tool for studying protein-mediated membrane fusion. Elucidation of the molecular mechanisms underlying virus-cell fusion may lead to a better understanding of the ubiquitous intracellular fusion events where specific proteins are also involved.

Entry of enveloped viruses into host cells: fusion activity of the influenza virus hemagglutinin

This volume contains the lectures presented at the NATO Advanced Study Institute (ASI) on "Trafficking of Intracellular Membranes: From Molecular Sorting to Membrane Fusion", held in Espinho, Portugal, from June 19 to June 30,1994. The objective of this Institute was to survey recent developments and to discuss future directions in the rapidly advancing field of membrane cell biology, with particular emphasis on the dynamical properties and intracellular flow of membranes. A wide range of interrelated topics around the central theme of intracellular trafficking of membranes was covered, including lipid flow, membrane fusion, dynamics of membrane components, protein folding and assembly, vesicular transport in membrane biogenesis, exocytosis and endocytosis. A large variety of experimental techniques and systems, including the application of viruses and model systems, to study these processes was also considered. Membrane cell biology is a broad discipline which encompasses many scientific areas including cell biology, biochemistry, biophysics, virology, immunonology and genetics. Indeed, recent advances in the cell biology of membranes could not have been made without this multidisciplinary approach. Significant progress achieved during the last few years in understanding how newly synthesized lipids and proteins find their way to the cell organelles, how molecular sorting and the continuous flow of membranes allow each cellular membrane to maintain its own distinct molecular composition, and, thereby, the individuality of the various intracellular compartments, was discussed in considerable detail in this Institute.

Traficking of Intracellular Membranes: From Molecular Sorting to Membrane Fusion: Proceedings of the NATO Advanced Study Institute

The functioning of the brain depends on the flow of information through elaborated circuits consisting of networks of neurons. Information is transferred from one cell to another at specialized points of contact, the synapses, where one nerve cell comes into appropriate apposition to its target cell.

Membrane Fusion in the Exocytotic Release of Neurotransmitters

Fusion activity of the influenza virus hemagglutinin does not require a transbilayer pH gradient

The apparatus can supply currents from 50 mu A to 4 mA with an output voltage up to 4 kV, suitable for very high impedance loads, much greater than 1 M Omega , such as the electrolyte cells used for moving boundary transference work.

https://iopscience.iop.org/article/10.1088/0022-3735/13/4/006/pdf

A high-voltage constant-current generator

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