Medicines in gel nanocapsules

Scientists have created unique nanocapsules for targeted drug delivery

MSU Press Service

An international group of researchers with the participation of physicists from Lomonosov Moscow State University has developed a completely new type of drug carrier for their targeted delivery to a diseased organ – gel nanocapsules with a double shell. The scientists published the results of their work in the journal Scientific Reports (Schmid et al., Multi-Shell Hollow Nanogels with Responsive Shell Permeability).

The research is still fundamental. However, one of the authors of the study, Igor Potemkin (professor of the Department of Polymer and Crystal Physics, Faculty of Physics, Moscow State University), claims that in the coming years, based on this work, it will be possible to create nanocapsules that will be ideal carriers for targeted drug delivery, and their production will be relatively cheap.

Scientists have been engaged in targeted drug delivery for a long time, many laboratories around the world are working on their creation, since the prospects for this direction are huge. Many "nanoequips" have been created to deliver medicines to the right address, but scientists still face many problems. The main one, many researchers believe, is the problem of how to get the medicine to start acting only when it gets to the right place.

"Many existing carriers encapsulate drugs due to long–range electrostatic interaction - the charge of the carrier is opposite to the charge of the drug. We don't have any electrostatics, everything here is controlled by temperature – both filling the internal cavity, and locking it, and releasing its contents where it is required. Therefore, the drugs themselves can be both charged and neutral," comments one of the Russian co–authors of the article, Doctor of Physico-Mathematical Sciences Igor Potemkin.

According to the authors of the article, there are other stimuli for the release of drugs, for example, an external magnetic field, the acidity of the medium (pH), but in each case, as in the case of electrostatics, researchers face the problem of premature release of drugs.

The scientists decided to use structures that had not been practically studied before – gel nanocapsules. The main problem that had previously sharply reduced interest in them was that such capsules, as soon as they appeared, immediately stuck together with their neighbors (lost colloidal stability) when trying to "load" them with medicines, which made delivery impossible (or ineffective). Scientists have managed to solve this problem by creating a carrier whose inner cavity, like an egg with two shells, is surrounded by two shells of different chemical composition. The outer porous shell plays a protective (stabilizing) role and prevents the adhesion of nanocapsules, and the pores of the inner shell can open and close depending on temperature due to changes in the interaction between its monomer units.

At the moment of filling the cavity, the pores are open, and the medicine is absorbed into it as into a sponge, then the temperature changes, the pores of the inner shell close, and the medicine goes on its way. In the future, the pores will be able to open again only where the temperature allows it.

Figure from an article in Scientific Reports

The preparation of two-layer capsules in this experiment was reduced to the layered synthesis of two polymer shells of different chemical composition around a silicon oxide core, and at the end of the synthesis, this core was chemically dissolved, leaving an empty space instead.

The main difficulty of this work was that the researchers largely went blind, not knowing for sure how their nanocapsule would behave, whether its cavity remaining after the removal of the silicon core would "collapse", whether the pores of the shells would be of sufficient size to suck in the transported substance and then release it there, where required, whether it will be securely locked during transportation. Fortunately, all these fears turned out to be in vain – in response to temperature changes, the pores opened and closed, "on the way" (in the experiment, there was no real "road" – scientists measured possible losses from the cavity as time passed), the contents of the capsules were practically not lost, and the inner cavity not only did not collapse – it it became even larger than the original size of the silicon core.

The manufacture of nanogel capsules and related measurements were carried out in Europe, mainly in Germany, and Russian scientists from Moscow State University, Igor Potemkin and his colleague Andrey Rudov, worked on computer modeling, with which researchers studied the dependence of the structure of nanocapsules on temperature. Also, MSU physicists using computer modeling demonstrated a method of encapsulation and release of transported molecules when temperature changes.

At this stage, the work was purely fundamental in nature and was intended primarily to demonstrate the effectiveness of the concept. The experiments were carried out in the temperature range of 32-42 °C. This is somewhat more than the temperature range favorable for humans, although in the future, Igor Potemkin claims, this range can easily be narrowed.

The joint work of the group is designed for another four years. "There are still many questions left," the scientist comments. – For example, we "caught" a structure in which the cavity does not collapse as it collapses (that is, at the time of pore closure). Now it remains to understand how this happens, how the crosslinking density of the layers affects, i.e. what is the minimum amount of the crosslayer that does not lead to the collapse of the cavity, and so on."

Potemkin is confident that in any case, the nanocontainers created by the research group are ideal carriers for targeted drug delivery. Moreover, their synthesis is not complicated and relatively cheap. Although it is difficult to name its specific cost at this stage of research, the plans of the collaboration already include the creation of a large-tonnage, commercially acceptable production of microgels.

Portal "Eternal youth" http://vechnayamolodost.ru  19.05.2016