Target Delivery

Drug targeting (as an important example for targeted cargo delivery) is defined as selective drug delivery to specific physiological sites, organs, tissues, or cells, where a drug's pharmacological activity is required. Target delivery technologies have been applied to drugs whose designated site of action is difficult to reach and also to cytotoxic compounds which must not reach sites other than the therapeutic sites in order to prevent cytotoxic side effects. There is currently no applied pharmaceutical treatment available that can be applied locally in a controlled way, thereby shielding healthy cells from drug interaction. Magnetic drug targeting has been suggested as a method to locally accumulate drugs. It has recently been shown in vivo that it is possible to direct drugs bound to magnetic nanoparticles to tumor tissue using magnetic field gradients.
Fig. 5. (a) Magnetic targeting of capsules for local accumulation. Capsules functionalized with magnetic NPs (black) are trapped in a magnetic field gradient created with a permanent magnet. Fluorescent NPs (green) in the capsule walls permit visualization by optical techniques. (b) Specific uptake of capsules by cells via molecular recognition. The surface of the capsules is functionalized with ligands that bind to corresponding receptors localized in the membrane of target cells.

The same concept can be applied for polyelectrolyte capsules whose walls are functionalized with magnetic nanoparticles (fig 5a). Specific accumulation of magnetic nanoparticle-functionalized polymer capsules in a magnetic field gradient, followed by capsule internalization by breast cancer cells has been recently demonstrated in vitro. By labeling the walls of the capsules with fluorescent nanoparticles (in addition to the magnetic nanoparticles), high local concentration and thus their drastically increased internalization along the field gradient could be easily observed with a fluorescence microscope. Although this method works reliably in cell cultures, it has to be pointed out that due to the technical challenge of focusing magnetic field gradients, this method does not work on a single cell level, but that accumulation of capsules can be enhanced at certain regions within the cell culture/tissue.

Naturally, the classical concept of targeted drug delivery via receptor-ligand interaction can also be applied to the capsules (fig 5b). For this purpose, ligands that specifically bind to receptors expressed by target cells are immobilized on the capsule surface, resulting in an increase in the uptake rate of capsules by target cells compared with surrounding cells. Unfortunately, all the complications and technical problems associated with molecular recognition-based drug delivery also apply to ligand-modified capsules. In particular, improved surface chemistries of the capsule walls (such as PEG) are certainly required in order to obtain sufficient retention time (the time for which the capsules are circulating in the blood stream until they are cleared from it by the organism). Nevertheless, these capsule-based systems are presented as drug carriers that allow for at least two parallel ways of targeting:

(i) local accumulation of capsules near the target tissue by attraction of magnetic nanoparticles in the capsule walls with magnetic field gradients and

(ii) enhanced uptake by target cells due to ligands attached to the surface of the capsule walls, which specifically bind to their receptors present on the outer membrane of the target cells.

In this way, the combination of two strategies within one carrier system is expected to lead to improved targeting and thus less unwanted delivery of drugs to surrounding tissue.