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Nanotechnology for Drug Targeting and Gene therapy
Selective delivery of drugs to specific areas in the body is necessary to minimize side effects. The magic-bullet concept represents an early description of drug targeting paradigm. Such targeting can be achieved at the organ level and the drugs may involve prodrugs (which release a drug at the targeted site), monoclonal antibodies and polymeric and colloidal carriers.

Nanotechnology involves the use of nanoparticles (<1mm, usually <500nm in diameter) used as particular carrier systems for drug delivery. These particulates include not only solid structures in the form of nanocapsules, but also includes liposomes and emulsions, that can reach specific tissues or even specific sites within a cell. They can be used for delivery of drugs, vaccine administration and for diagnostic imaging.

Designing of targeting system, keeping in view the fate of nanoparticles after intravenous administration
A targeting system needs to be appropriately designed keeping in view the fate of nanoparticles after intravenous administration. After the particles are injected into the blood stream, they are conditioned or coated by elements like plasma proteins and glycoproteins available in the circulatory system. This process is called opsonization, which renders the particles recognizable by the major defense system of the body. The macrophage cells (called Kupffer cells) of the liver and other macrophages remove these opsonized particles.

Particles having hydrophobic surface are more efficiently coated, but those having hydrophilic surface resist this coating and are therefore cleared more slowly. Therefore, nanoparticles having hydrophilic surfaces, should be preferred for gene therapy.

Passive targeting of nanoparticles.
Although uptake of nanoparticles by Kupffer cells may be a hindrance in delivery of drug to the target, atleast in some cases, this feature can be exploited to help treatment. This is true in cases, where the macrophages themselves are directly involved in the disease process, as in case of leishmaniasis, listeria and candasis. In other cases, capture and degradation of nanoparticles by macrophages can exploited to achieve the controlled delivery of drugs to the blood circulation. This is because through macrophages the particles reach endosomes and then to lysosomes, where they are degraded, so that the drug is released and diffused into the circulatory system.

This strategy can be applied in the delivery of anticancer agent adriamycin, and antifungal agent amphotericin.

In cases, where capture by Kupffer cells is a barrier to the targeting of drug, the particles may bedisguised, so that they are no longer recognized by Kupffer cel1s and therefore escape capture by them. The nanoparticles can be disguised partly by making them hydrophilic and partly by stabilizing them using absorbed polymers. Nondegradable polystyrene, polyoxy­ethylene or a block copolymer are some such adsorbed polymers, which do not allow recognition of liposome  by macrophages and thus prevent opsonization so that the nanoparticles persist within the circulation. Such stealth liposomes are undergoing clinical trials for tumour targeting.

Active targeting of colloidal carriers.
Targeting ligands (e.g. monoclonal antibodies, sugar residues, etc.) can also be attached to nanoparticles to achieve active targeting of these particles. The hepatocytes of liver can be an important target in case of hepatitis and also in other cases of gene therapy, when administered gene needs to be expressed in these cells of the liver. The nanoparticles having ligands for active targeting, should not only escape captive by kupffer cel1s of the liver, but also need to be small enough (>50nm or even >20nm in size) to be able to enter the hepatocytes with the help of specific receptors on these surfaces and through ferestrations that are 100-150 nm in diameter.