For the first time, an effect of detonation nanodiamonds (NDs) with different surface compositions on the main functional characteristics of isolated rat liver mitochondria was studied. The response of membrane potential, calcium retention capacity, and redox state of pyridine nucleotides have been monitored upon the administration of NDs functionalized with carboxyl, hydroxyl, amine, hydrogen, and chlorine surface groups. Hydrogenated and chlorinated NDs caused reduction of the membrane potential and calcium retention capacity of mitochondria. An aminated ND caused an even greater decrease in calcium retention capacity (at a concentration of 0.75 mg/ml), reducing it to 65% of the control. The use of cyclosporine A prevented a decrease in membrane potential and calcium retention capacity indicating the induction of non-specific mitochondrial membrane pores during the NDs incubation with mitochondria. Hydrogenated and chlorinated NDs had no significant effect on the redox state of mitochondrial pyridine nucleotides. Other NDs studied had no effects on functional characteristics of mitochondria, even at high concentrations (up to 1.5 mg/ml). High activity of chlorinated and hydrogenated NDs may be due to the greater hydrophobicity of their surface and its interaction with mitochondrial pores components. Thus, isolated rat liver mitochondria can be used as a biomodel for initial testing of ND samples to assess the possibility of their use in drug delivery systems.
The effect of the chemical nature of the surface of detonation nanodiamond on the adsorption of an antibiotic is revealed with the help of tritium-labeled amikacin. It is found that nanodiamonds with a carboxylated surface (Ssp = 283 ± 5 m2/g) chemisorbed twice as much amikacin as nanodiamonds with a hydrogenated surface (Ssp = 289 ± 5 m2/g): 48 and 22 mg/g, respectively. Maintaining nanodiamonds with immobilized amikacin in the form of hydrosol for 1 month results in a release of up to 9.6 and 6.4 mg/g of the antibiotic, respectively. The results demonstrate the possibility of creating an amikacin delivery system based on nanodiamonds.
Detonation nanodiamonds (NDs) with chlorinated (ND-Cl) and carboxylated (ND-COOH) surfaces were obtained. The broad-spectrum antibiotic Amikacin (Amik) was covalently grafted to the chlorinated surface (ND-Amik) and immobilized by adsorption to carboxylated surface (Amik/ND-COOH). Biological testing in vitro showed the presence of antibacterial activity of the obtained samples against Staphylococcus aureus FDA P209 and Escherichia coli ATCC 25922, close to activity of free amikacin. It was revealed that to maintain antibacterial activity of the samples after their preliminary treatment, important factors such as the use of antioxidants (hydrosulfite and sodium citrate) and lyophilization were necessary.
In recent years, detonation nanodiamond is regarded as a promising material for biomedical applications. However, a significant problem that stops of intensive development of this area is a absence of commercial NDs standardization. This article presents the results of the study of physicochemical properties of several industrial nanodiamonds available in the international market. The differences of physicochemical characteristics of nanodiamonds produced, selected and purified in various ways are shown. A method is developed for industrial processing of nanodiamonds, that represents high-temperature hydrogenation of diamond surface and allows to unify their properties. It is shown that after these processing nanodiamonds have the same surface chemistry and can form stable hydrosols. The proposed method of industrial nanodiamonds unification can become a universal method of its standardization.
Analysis of published and author's own experimental data provides convincing evidence for the theoretical possibility to create drug delivery systems on the basis of detonation nanodiamonds and for the promise such systems hold for commercialization and practical application.