Method for introducing gold nanoparticles by local skin application

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutical industry and represents a method for introducing gold nanoparticles into the body by the local skin application, differing by applying the preparation of the following composition: 96% dimethyl sulphoxide 0.1 ml per a gel base 1 ml with gold nanoparticles d=140 nm, or the preparation of the following composition: 20% thiophane sulphoxide 0.1 ml per a gel base 1 ml with gold nanoparticles d=40 nm; the skin areas coated with gold nanoparticles in complex with organic sulphur compounds shall be exposed to ultrasound at frequency 1 MHz, power 2 Wt and length 2 minutes.

EFFECT: invention provides higher transdermal permeability of gold nanoparticles and no nanoparticle accumulation in the internal organs.

8 dwg

 

The invention relates to medicine, in particular to Oncology, dermatology, cosmetology, veterinary medicine and can be used in the development of drugs for the treatment of superficial skin tumors.

To date, published a large number of studies on the use of gold nanoparticles in various fields of medicine[8, 9, 10, 11]. Among the treatment means there are medications, which included particles of gold or its compounds. The gold nanoparticles are haptens and antigens, enhance immune response and are carriers of vaccines and pharmaceutical agents for delivery to the organism [12]. It is known that gold has anti-inflammatory, immunodepressants, antitumor, antifermentny and some other therapeutic effects. Gold preparations used in the treatment of patients with rheumatoid and psoriatic arthritis, a syndrome still's, lupus erythematosus[13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Studies have shown high efficiency of the use of nanosized particles of gold in the treatment of malignant tumors of the skin and its appendages using controlled local hyperthermia in the experiment [4, 5].

Investigated parenteral route of administration of gold nanoparticles in the organism of animals and humans, as well as the kinetics of distribution of nanoca the TIC gold in internal organs [1, 2, 3, 33]. However, this way of introducing themselves soluble dosage form nanoparticles have a number of side effects. Along with the positive, therapeutic effects of their accumulation in tumor tissues, including skin epidermal observed and negative - of their accumulation in the internal organs (liver, spleen, lungs, kidneys), lead to the violation of organ and tissue microcirculation, the development of degenerative changes [1, 2].

Currently, there are no alternative methods of administration of nanoparticles for efficient accumulation in the skin and subcutaneous tissues, while their transdermal transport can be provided with some organic sulfur compounds, facilitating the transfer of high-molecular compounds, molecules whose dimensions are far superior to the used nanoparticles.

Given the high level of security and accuracy of local injection of the nanoparticles directly into the fabric of epidermal tumors in situ, with the exception of the side effect of accumulation in the internal organs, there is an actual use of nanoparticles in complex with compounds that enhance their transdermal diffusion.

The technical result from the use of this invention is to increase the transdermal permeability of the gold nanoparticles and the absence of negative side effects (the accumulation in the internal organs (liver, spleen, lungs, kidneys).

The claimed technical result is achieved in the following way: on the skin applied:

1) 0.1 ml of 96% solution of DMSO per 1 ml of gel base gold anacleto d=140 nm;

2) 0.1 ml of 20% solution of thiophencarboxylic 1 ml gel base gold anacleto d=140 nm

To improve transdermal permeability additionally use phonophoresis [6]. The skin after the application of gold nanoparticles in complex with organic sulfur compounds is subjected to ultrasound with a frequency of 1 MHz, a power of 2 W and a duration of 2 minutes (ultrasonic emitter "Dinatron 125," the company Dinatronics.Co, USA).

The method of introducing gold nanoparticles by topical application onto the skin can be used to develop dosage forms drug nanoparticles for cosmetology, treatment of cancer of the skin in medicine and veterinary medicine.

The analysis of descriptions of inventions to patents, selected when conducting a patent search, and patent research conducted found that dosage forms and formulations for topical application to the skin containing gold nanoparticles in combination with organo-sulfur compounds in the patent literature are not met. On the basis of what can be considered that different solutions could the t to be patentable and decorated claims. Therefore, the claimed invention meets the condition of "novelty."

The authors first examined the transdermal permeability of intact and damaged skin for gold nanoscale materials in complex with organic sulfur compounds. At the same time managed to avoid the side effects of the accumulation of nanoparticles in the internal organs (liver, spleen, lungs, kidneys), disturbance of organ and tissue microcirculation, the development of dystrophic changes that are commonly observed when intravenous injection [6].

In the study was used male outbred albino rats, the weight of which averaged 150-200 grams. The animals were kept in accordance with the "Rules of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes". After the hair on the back of each rat were markings on the skin of animals from each group was allocated a land plot, on which was applied the gel with nanoparticles and a solution of dimethyl sulfoxide, or thiophencarboxylic, and then was subjected to ultrasonic impact.

The results were evaluated by the following methods:

1) classical histological technique with the manufacture of microscopic specimens of skin and organs and standard color (Fig.1-4).

The figure 1 presents the structure of the tour epithelium of the skin of animals of the experimental group No. 4. Paint hematoxylin-eosin, ×600. - gold particles on the surface (1), and penetrating into the dermis (2). In the figure 2. shows the structure of the epithelium of the skin of animals of the experimental group No. 6. Paint hematoxylin-eosin, ×600 - gold particles on the surface (1), and penetrating into the dermis (2). In the figure 3. shows the liver of animals from the control groups, colouring hematoxylin-eosin, ×600. On the figure 4 - the spleen of animals from the control groups, colouring hematoxylin-eosin, ×600;

2). staining of histological preparations of silver nitrate (5, 6).

The figure 5 presents the skin of animals of the experimental group No. 4, color silver nitrate, ×600, in figure 6 - leather of animals of the experimental group No. 5, colour silver nitrate, ×600;

3) optical coherence tomography (Fig.7, 8)

The figure 7 presents the OCT tomograms skin of rats experimental group No. 4 figure 8 - OCT-tomogram plot of the experimental group No. 6.

According to light microscopy varying degrees of increase, on the preparations of the skin of animals subjected to ultrasonic impact, as with the application of only one gel, and in combination with organic sulfur compounds, you can see that organic sulfur compounds and ultrasonic effects contribute to the increased permeability of nanoscale materials through transdermal is arier (1, 2, 5, 6). The local application of substances, either in the liver or spleen nanoparticles were not detected (Figure 3, 4).

As can be seen from Fig.7, 8 there has been a significant increase in contrast that indicates penetration of the gold nanoparticles into the fabric. Thus, organic sulfur compounds and ultrasonic effects enhance the diffusion of the nanoparticles.

The method of introducing gold nanoparticles in the body by topical application to the skin, wherein the drug is applied following composition: 0.1 ml of 96%-aqueous solution of DMSO per 1 ml of gel base with gold nanoparticles (d=140 nm, or preparation of the following composition: 0.1 ml of a 20%aqueous solution of thiophencarboxylic 1 ml gel base with gold nanoparticles (d=140 nm, while the skin after the application of gold nanoparticles in complex with organic sulfur compounds should be subjected to ultrasound with a frequency of 1 MHz, a power of 2 W and a duration of 2 minutes



 

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