Diffusion of Univalent Ions Across the Lamellae of Swollen Phospholipids

Liposomal drug delivery systems: from concept to clinical applications.

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

Strategies in the design of nanoparticles for therapeutic applications

Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1−100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.

Impact of Nanotechnology on Drug Delivery

The action of steroids and streptolysin S on the permeability of phospholipid structures to cations.

The recognition that biological cells exploit the surface-active properties of lipids to define anatomical membranes has, in recent years, encouraged many workers to develop and study model systems based upon the orientation of lipids at interfaces (Bangham 1963). A considerable advance was made when Mueller, Rudin, TiTien and Wescott (1964) and Haydon (quoted in Taylor 1963), simultaneously and independently reported a technique for the preparation of isolated bimolecular lipid membranes separating two aqueous compartments. Such preparations, although some­what fickle, have enabled a variety of physical parameters to be measured. The technique lends itself pre-eminently to electrical studies of a.c. and d.c. resistances and of capacitance (Thompson 1966, Hanai, Haydon and Taylor 1964). The major criticism of the technique, however, is that the precise composition of the “black” (bimolecular) membrane is in some doubt, since it has not been found possible to spread the membranes in the absence of a relatively large mole fraction of a “filler” hydrocarbon and of water insoluble solvents. Indeed, according to Clements and Wilson (1962), if as little as 1 % of the lipid mass in a membrane contains non-polar compounds, e.g. chloroform, the membrane may be considered to be in a fully anaesthetized state. A further difficulty is encountered when lipid mixtures analogous to those present in biological membranes fail to produce useful membranes.

A.D. Bangham

Papers

Diffusion of Univalent Ions Across the Lamellae of Swollen Phospholipids

The action of steroids and streptolysin S on the permeability of phospholipid structures to cations.

The Diffusion of Ions from a Phospholipid Model Membrane System