29 October 2021

Safe nanocellulose

Nanocrystals will deliver the medicine exactly to the target

"Scientific Russia"

A group of scientists from the Komi Scientific Center of the Ural Branch of the Russian Academy of Sciences (Institute of Chemistry, Institute of Physiology, Institute of Biology) and the National Medical Research Center of Hematology of the Ministry of Health of Russia evaluated the suitability of different types of cellulose nanocrystals for use in the drug delivery system.

An article with the results of the study was published in the journal Carbohydrate Polymers (Torlopov et al., Hemocompatibility, biodegradability and acute toxicity of acetylated cellulose nanocrystals of different types in comparison).

One of the key problems of modern pharmacology is the need for targeted delivery of medicines to the lesion. This is especially important for the treatment of oncological diseases, when it is necessary to purposefully affect the tumor without affecting healthy tissues. For the first time, the great German immunologist Paul Ehrlich thought about the search for a "magic bullet" at the end of the XIX century. In the XXI century, nanotechnology came to the aid of doctors.

"In order to increase the concentration of the active principle in the target organ, drugs are combined with nanostructures – particles, complexes, crystals, gels, that is, they are used as a means of delivery," says Natalia Drozd, one of the authors of the work, a leading researcher at the NMIC of Hematology. "In combination with nanoscale structures, drugs penetrate cell membranes much better, and the active principle reaches the target organ in greater quantities."

Delivery vehicles must be non-toxic, biodegradable and compatible with body tissues. The researchers tested whether acetylated cellulose nanocrystals of different shapes have these properties: disc-shaped and two types of columnar.

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Micrographs of nanocrystals (scanning atomic force microscopy).

Solutions of nanocrystals of different concentrations were kept in vitro with blood or plasma, then standard tests were carried out: clotting time, activated partial thromboplastin time, prothrombin time, thrombin time. Ideally, the delivery system should have no effect on the blood. Such tests are also used to assess the hemocompatibility of materials that come into contact with blood indirectly, for example, blood storage containers. The analysis showed full compatibility of all types of nanocrystals studied with blood.

The toxicity analysis of the new structures was carried out using experimental animals. An aqueous solution of nanocrystals was administered orally to mice. All the studied substances showed their non-toxicity and did not affect the condition of internal organs. The solutions were administered intravenously to rabbits at the rate of 1 mg per 1 kg of weight. The solutions did not cause platelet aggregation, did not destroy the erythrocyte membrane, and had no effect on plasma clotting time.

Thus, all the studied types of acetylated cellulose nanocrystals — both columnar and disc—shaped - have shown their non-toxicity and hemocompatibility. However, disc-shaped nanocrystals decompose better under the action of enzymes, which makes them very promising for further development as a means of targeted drug delivery.

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The next step should be the study of cellulose nanocrystals in combination with anti-cancer or anti-inflammatory drugs.

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