RU2381030C2 - Method for administration of magnetic nanoparticles for local therapy in diseases of organism in experiment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: tissues of an organism are coated with a substance presented by ferrihydride nanoparticles prepared of cultivation of bacteria Klebsiella oxytoca which are recovered from sapropel of Borovoe lake, the Krasnoyarsk Territory. Application of the substance is followed with exposure to the external magnetic field during 30 minutes.

EFFECT: deeper penetration of nanoparticles into the tissue.

6 dwg

Description

The invention relates to medicine and can be used for local therapy for various diseases of the body.

A known method of introducing magnetic nanoparticles into the body of mice using a magnetic field gradient, where the iron-containing nanosubstance is administered intravenously and is exposed to an external magnetic field / 1 /.

The disadvantage of this method is the high concentration of nanosubstances and systemic toxic effects of the drug on the body.

In addition, there is a method of topical application of magnesium nanoparticles in the form of an ointment to improve tissue healing / 2 /.

The disadvantage of this method is the lack of magnetic properties of the nanosubstance, which can be controlled by an external magnetic field.

The objective of the proposed method is to assess the ability of magnetic nanoparticles to penetrate into body tissues for local therapy for diseases. The task is achieved due to the fact that the substance of the iron-containing compound is applied to the body tissues and is exposed to an external magnetic field.

Magnetic nanoparticles of Fe ₂ O ₃ · nH ₂ O ferrihydrite were obtained as a result of cultivation of the Klebsiella oxytoca bacteria isolated from the sapropel of Lake Borovoye - Krasnoyarsk Territory. The sapropel selected in the lake was passed through a magnetic separator. Microorganisms thus isolated were dispersed onto an agar medium and grown to obtain colonies. The biomass grown in a liquid medium was checked for the presence of magnetic particles on an FMR spectrometer. To isolate magnetic nanoparticles, the biomass was separated by centrifugation (10 min, 10,000 rpm) and destroyed on an ultrasonic disintegrator UZDN (1 min, 44 kHz, 20 kW). The resulting precipitates were dried at a temperature of 60-80 ° C.

Ferrihydrite Fe ₂ O ₃ · nH ₂ O is an antiferromagnet. Due to the small particle size (d <100 Å), the magnetic moments of Fe ³⁺ ions located on the surface of the particle turn out to be uncompensated and form a “spurious” integral magnetic moment of an individual particle.

In the present experiment, the Polyus-101 apparatus for low-frequency magnetotherapy was used as a source of an external magnetic field, which provided continuous operation of one inductor (1.5 ± 0.3 mT).

To determine the penetrating power of magnetic nanoparticles, an in vitro study was performed on the remote mucous membrane, cartilage and bone tissue of a person. To identify nanosubstances in the materials, a histological examination was performed using the Perls reaction / 3 /.

Pieces of the removed mucous membrane, cartilage and bone tissue were placed in a flask with dissolved iron-containing nanoparticles for 10 min, then the flask was placed in a magnetic field created by the Pole-101 apparatus for 10, 20, and 30 min (different samples), and then washed in saline and sent for histological examination.

As a control, studies were carried out of the penetration of nanoparticles into tissues without magnetic effects.

A study was conducted in 20 experiments on human tissues.

In a series of experiments on the mucous membrane without magnetic influence, the nanoparticles were on the surface of the epithelium (Fig. 1).

When the material was introduced into the magnetic field for 10 min, the activity of the nanoparticles increased significantly, which was characterized by their penetration into the mucous membrane, and after 20 and 30 minutes into the submucous layer of the multi-row cylindrical epithelium (figure 2).

When conducting an experiment with cartilage tissue without magnetic action, the nanoparticles also did not penetrate into the thickness of the cartilage (figure 3). Figure 3 shows that the iron-containing particles are located in the surface layer in the form of a "chain". Under the action of an external magnetic field, the nanoparticles were randomly distributed over the entire length in radial directions. Moreover, with an increase in the time of magnetic action from 10 to 30 min, the number of penetrated nanoparticles increased (Fig. 4).

In a series of experiments with bone tissue without a magnetic field, the distribution of iron-containing particles was along the edge of the bone beams, i.e. without penetrating deep into (figure 5). Under the gradient of the magnetic field of the nanoparticles diffusely penetrated into the thickness of the bone tissue, spreading to its entire depth (Fig.6). The duration of magnetic action contributed to the increase of nanoparticles from single after 10 minutes to mass penetration after 30 minutes.

Thus, the experiments performed on human tissues make it possible to evaluate the ability of local penetration of iron-containing nanoparticles into the body using low-frequency magnetotherapy, which indicates the possibility of local administration of magnetic nanoparticles for therapy in diseases of the body.

Used Books

1. RF patent No. 2166751, G01N 27/12, 33/53, Bull. No.13, 05/10/2001

2. RF patent №2306141, А61К 33/06, Bull. No.26.09.09.2007

3. Avtandilov G. G. Fundamentals of quantitative pathological anatomy / G.G. Avtandilov. - M .: Medicine, 2002 .-- 240 p.

Claims (1)

A method of introducing magnetic nanoparticles into tissues for conducting local therapy for diseases of the body in an experiment, including the use of iron-containing nanoparticles and an external magnetic field source, characterized in that the iron-containing nanoparticles, represented by ferrihydrite nanoparticles obtained by culturing the bacteria Klebsiella oxytoca isolated from sapropel Lake Borovoe Krasnoyarsk Territory, applied topically to body tissue and exposed to an external magnetic field for 30 minutes.

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