Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects.

Marina V Novoselova,Sergey V German,Oleg A Kulikov,Mikhail N Zharkov,Olga V Minaeva,Nikolay A Pyataev,Gleb B Sukhorukov,Ekaterina P Brodovskaya,Valentin P Ageev,Dmitry A Gorin,Olga A Sindeeva

doi:10.3390/polym11061082

Abstract

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.

Highlights

In the past decade, the development of effective carriers of bioactive compounds for use in preventive and personalized medicine has received considerable research attention.Ideally, a carrier should have the following characteristics: sufficient drug loading capacity, high potential for accumulation in the diseased tissue, controlled drug release kinetics, biological inertness and complete biodegradation [1].Polymers 2019, 11, 1082; doi:10.3390/polym11061082 www.mdpi.com/journal/polymersA possible approach to making such composite carriers is sequential adsorption of polyelectrolytes from solutions on the surface of template spherical particles of calcium carbonate, with subsequent dissolution of the latter [2,3]
We can observe a moderate but statistically significant increase in the level of aspartate aminotransferase (AsT) and lactate dehydrogenase (LDH), as well as a tendency for an increased creatine phosphokinase (CPK) level in the group receiving MNPs(BSA–tannic acid (TA))
The possibility of particle navigation under the action of an external magnetic field gradient was demonstrated with carriers containing high concentrations of MNPs and the Cy7 dye inside the core

Summary

Introduction

A possible approach to making such composite carriers is sequential adsorption of polyelectrolytes (layer-by-layer, LbL) from solutions on the surface of template spherical particles of calcium carbonate (vaterite), with subsequent dissolution of the latter [2,3] The size of these carriers determines the in vivo accumulation and translocation and the biological fate and toxicity of these delivery systems. Control of particle size provides a means of tuning drug release rates [5] From this standpoint, an undoubtedly important and promising task is to adapt and optimize the proposed approach to the effective adsorption of a preparation to submicron carriers. An undoubtedly important and promising task is to adapt and optimize the proposed approach to the effective adsorption of a preparation to submicron carriers This would make it possible to overcome a number of problems related to the dimensional characteristics of composite microcarriers

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