The magic bullet: heat-seeking drugs

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http://www.elpais.com/articulo/sociedad/The/magic/bullet/heat-seeking/drugs/elpepusoc/20120131elpepusoc_1/Tes

The magic bullet. Scientists in the sixties believed they had discovered this when they prepared small bubbles composed of natural components of the cell membrane. These artificial vesicles, named liposomes, can be made simply by mixing natural lipid molecules. This leads to liposomes with an aqueous interior forming spontaneously. Drugs can easily be incorporated in the interior of the liposomes, raising the possibility that drugs can be transported specifically to their target. Such a drug delivery strategy would improve therapy, especially in cancer treatment where the patients' life quality is significantly compromised by the severe systemic side effects of conventional treatment.

In fact, the optimistic view of early researchers has not been translated into clinical practice as yet. More than 40 years later, only a few liposomal drugs are approved. However, none of these have shown an increased antitumor effectivity compared to free drug and approval was granted due to a reduction in specific organ toxicity only. The main cause for the initial failure of liposomes was the unsolved problem of triggered drug release. The liposomes have to be chemically stabilized in order to prevent rapid degradation after intravenous application. This leads to liposomes with very long plasma circulation half lives. Since the tumor vessels - but not the surrounding, healthy vessels - are leaky, the circulating liposomal drugs passively leak into and hence accumulate in the tumor tissue. However, despite this accumulation at the tumor target, there is not sufficient drug release out of the carrier system.

A method is required to trigger release of the active drug from its liposome carrier. In 1978, the principle using heat was first established. Liposomes are synthesized from phospholipids, which have a unique chemical structure that allows a change in aggregate state from solid to fluid at a distinct temperature. This results in liposomes becoming "leaky" when increasing the body temperature from 37 to 41 °C in the target area, in theory releasing the drug at the target location. It has taken more than 20 years for such temperature-sensitive liposomes to be developed and tested successfully in animals. However, these liposomes - designed at Duke University in the USA - suffer from insufficient stability at body temperature, resulting in a significant loss of their payload before reaching the target.