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High-capacity CaCO3 containers: the effect of size on drug loading and interaction with cells
1 , 1 , 2 , 2 , 3 , 3 , 4 , * 1, 4
1  A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences
2  Ioffe Institute
3  Institute of Chemical Biology and Fundamental Medicine (ICBFM), Siberian Branch of Russian Academy of Sciences (SB RAS)
4  I.M. Sechenov First Moscow State Medical University
Academic Editor: Amélia Pilar Rauter

Published: 07 November 2022 by MDPI in 8th International Electronic Conference on Medicinal Chemistry session General

Series of calcium carbonate particles with sizes of 500 ± 80 nm and 200±90 were obtained by the mass crystallization in aqueous salt solutions by varying the reaction conditions and adding glycerol or combination of polyethylene glycol, polysorbat-80 and cell cultural medium to the reaction volume. Calcium carbonate nanoparticles of 50±30 nm in diameter were synthesized within the pores of mesoporous silica particles with a subsequent etching out of the template material. A complete characterization of the particles was carried out using scanning and transmission electron microscopy, X-ray powder diffraction, dynamic and electrophoretic light scattering. CaCO3 particles were loaded with anticancer drugs, porphyrazine and doxorubicin, with an encapsulation efficiency of 2-5 and 4-11 wt.%, respectively. The spontaneous release at pH 7 reached 15%, and when the particles are dissolved at pH 4, the release was about 45% of the substance during the day, regardless of the encapsulated substance. Functionalization of the surface of calcium carbonate particles with a biocompatible Pluronic-folic acid conjugate did not affect the particle size distribution and aggregative stability for all three samples. The effect of coatings on the rate of internalization and accumulation of particles by cells expressing folic acid receptors was established. It was also shown that the internalization of 50 ± 30 nm particles was more active than other samples.

The work supported by the Russian Science Foundation (Project #21-74-10058).

Keywords: calcium carbonate nanoparticles, high-capacity containers, porphyrazine, doxorubicin, targeted drug delivery