17 March 2008

Micro-needles that make life easier

Trusov L. A., NanometerFor the treatment of diseases, it is necessary to deliver certain medications to the body.

It would be great if all medications could be taken orally – but, unfortunately, some substances decompose in the aggressive environment of the gastrointestinal tract, others do not penetrate well into the blood, and others, even after entering the bloodstream, are filtered out by the liver, never reaching the target.

Another great option is the delivery of medicines directly through the skin. Everyone knows nicotine and hormonal patches, the use of which is effective and is not associated with pain. However, this method is only good for small and lipophilic molecules.

That is why a huge number of medications are administered to patients by subcutaneous injections. At the same time, there is a risk of infection of the wound, it is necessary to use sterile equipment and always have fresh medications, and poor patients (already sick!) they also suffer from the pain of injections. Some might dismiss these problems as unimportant, but not scientists from the Georgia Institute of Technology. To alleviate human suffering, they came up with a method of subcutaneous administration of medications with the least damage to the skin.

The proposed method of delivery of substances through the skin combines the effectiveness of injection and the painlessness of the patch. Hundreds of micrometer-sized polymer needles contain medicine. After their introduction into the skin, they quickly dissolve, and the drug diffuses into the skin.

Microneedles consist of polyvinylpyrrolidone (polyvinylpyrrolidone, PVP). Monomeric vinylpyrrolidone is a liquid (under experimental conditions), and the drug of interest can be added to it. Then such a mixture is poured into a pre-made mold, and vinyl pyrrolidine polymerizes under the action of ultraviolet light (Figure 1).

Figure 1. Production of arrays of polymer micro-needles.

1: micro-needles made of SU-8 photosensitive epoxy resin were obtained by photolithography;
2: a polydimethylsiloxane (PDMS) matrix is made on their basis;
3: a mixture of liquid monomer and drug is applied to the matrix;
4: the excess solution was removed so that the medicine was contained only in microneedles;
5: monomer was poured on top, without medication;
6: polymerization occurs under the action of ultraviolet light.

According to the authors, the PDMS matrix obtained once can be used repeatedly to manufacture arrays of micro-needles without losing the quality of the latter.

PVP has long been used in clinical practice, and therefore it can be considered safe for health. In addition, PVP is perfectly soluble in water – thus, when injected into the skin, the micro-needles then quickly disappear. The resulting needles measuring 750 microns in length, 250 microns in diameter at the base and 5 microns in radius at the top (Figure 2), containing various compounds as a model drug, were tested on pig skin in vitro.


Figure 2. Array of micro-needles from PVP containing sulforodamine as a model drug. a – top view; b – side view.

Approximately 1 minute after injection into the pig's skin, the arrays of microneedles completely dissolved. In one of the experiments, fluorescently labeled bovine serum albumin (this is a protein) was taken as a model drug, thanks to which they were able to trace the fate of the compounds introduced together with the microneedle. Figure 3 (left) shows that the microneedle has completely dissolved, and the model drug (fluorescently labeled bovine serum albumin) has penetrated into the deep layers of the skin.

In another case, an enzyme (β-galactosidase) was enclosed in microneedles. It was shown that the enzyme not only penetrated the skin, but also retained its activity at the same time (Figure 4, right). Beta-galactosidase cleaves the X-gal substrate to form a colored product. The appearance of a blue spot indicates the presence of an active enzyme.

One of the desired properties – the ability to deliver substances through the skin – arrays of micro-needles undoubtedly possess. The situation with painlessness is unclear: experiments seem to have been conducted exclusively on pig skin and only in vitro, but the authors confidently say that it does not hurt. Who knows, maybe they couldn't resist and experienced the novelty for themselves…

Portal "Eternal youth" www.vechnayamolodost.ru17.03.2008

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