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Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity.

Galagudza MM, Korolev DV, Sonin DL, Postnov VN, Papayan GV, Uskov IS, Belozertseva AV, Shlyakhto EV - Int J Nanomedicine (2010)

Bottom Line: Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery.Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells.Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Medicine, VA. Almazov Federal Heart, Blood and Endocrinology Center, St-Petersburg, Russian Federation. galagoudza@mail.ru

ABSTRACT
The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

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Related in: MedlinePlus

Aerosil surface functionalization using chemical assembly method.
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f3-ijn-5-231: Aerosil surface functionalization using chemical assembly method.

Mentions: The standard pyrogenic highly dispersed silica (Aerosil® of A170, A300, and A380 marks obtained from Vekton™, St Petersburg, Russia) was used throughout the experiments. The surface area of SNP was determined using the Brunauer–Emmett–Teller (BET) method and averaged from 170 to 380 m2/g. The mean particle diameter varied from 6 to 13 nm. The technique of SNP functionalization included three sequential steps: modification of SNP with (3-aminopropyl)triethoxysilane, hydrolysis of unreacted alkoxysilane groups, and binding of fluorescein. Chemosorption of (3-aminopropyl)triethoxysilane was performed from the gaseous phase with use of dried nitrogen as a carrier gas. The synthesis was done in the vertical quartz flow reactor at 220°C for 2 hours. Hydrolysis of the unreacted alkoxysilane groups was achieved with water vapor at 150°C for 1 hour. The covalent binding of fluorescein to the aminated silica was done using carbodiimide technique for 1 hour (Scheme 1 and 2). All chemicals were purchased from Sigma-Aldrich Chemical Co (Moscow, Russia). The surface reactions were controlled with infrared spectroscopy (diffuse reflection) (Perkin–Elmer 1760×). The amount of fluorescein bound to the surface of SNP was determined spectrophotometrically at λ = 490 nm. Fluorescein content within the samples of modified SNP varied from 0.01 to 0.02 mM/g. Another fluorescent dye that can be used for labeling of SNP is considered to be indocyanine green (ICG). This fluorophore has an absorption band in the near-infrared region (λ = 780 nm). We have developed the technique of indocyanine green immobilization on the surface of aminated silica. First of all, it has been established that the sample obtained is stable in the saline to be used for the evaluation of nanoparticle biodistribution. Then, fluorescently labeled SNP were used for biodistribution studies (see below).


Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity.

Galagudza MM, Korolev DV, Sonin DL, Postnov VN, Papayan GV, Uskov IS, Belozertseva AV, Shlyakhto EV - Int J Nanomedicine (2010)

Aerosil surface functionalization using chemical assembly method.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865018&req=5

f3-ijn-5-231: Aerosil surface functionalization using chemical assembly method.
Mentions: The standard pyrogenic highly dispersed silica (Aerosil® of A170, A300, and A380 marks obtained from Vekton™, St Petersburg, Russia) was used throughout the experiments. The surface area of SNP was determined using the Brunauer–Emmett–Teller (BET) method and averaged from 170 to 380 m2/g. The mean particle diameter varied from 6 to 13 nm. The technique of SNP functionalization included three sequential steps: modification of SNP with (3-aminopropyl)triethoxysilane, hydrolysis of unreacted alkoxysilane groups, and binding of fluorescein. Chemosorption of (3-aminopropyl)triethoxysilane was performed from the gaseous phase with use of dried nitrogen as a carrier gas. The synthesis was done in the vertical quartz flow reactor at 220°C for 2 hours. Hydrolysis of the unreacted alkoxysilane groups was achieved with water vapor at 150°C for 1 hour. The covalent binding of fluorescein to the aminated silica was done using carbodiimide technique for 1 hour (Scheme 1 and 2). All chemicals were purchased from Sigma-Aldrich Chemical Co (Moscow, Russia). The surface reactions were controlled with infrared spectroscopy (diffuse reflection) (Perkin–Elmer 1760×). The amount of fluorescein bound to the surface of SNP was determined spectrophotometrically at λ = 490 nm. Fluorescein content within the samples of modified SNP varied from 0.01 to 0.02 mM/g. Another fluorescent dye that can be used for labeling of SNP is considered to be indocyanine green (ICG). This fluorophore has an absorption band in the near-infrared region (λ = 780 nm). We have developed the technique of indocyanine green immobilization on the surface of aminated silica. First of all, it has been established that the sample obtained is stable in the saline to be used for the evaluation of nanoparticle biodistribution. Then, fluorescently labeled SNP were used for biodistribution studies (see below).

Bottom Line: Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery.Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells.Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Medicine, VA. Almazov Federal Heart, Blood and Endocrinology Center, St-Petersburg, Russian Federation. galagoudza@mail.ru

ABSTRACT
The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

Show MeSH
Related in: MedlinePlus