Vaterite particles: Influence of their size and shape on drug loading and release
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Sechenov First Moscow State Medical University, Moscow, Russia
Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, Moscow, Russia
Publication date: 2021-09-27
Public Health Toxicol 2021;1(Supplement 1):A47
The latest advances in nanomedicine are aimed at targeted delivery of drugs to tumor foci after intravenous administration with the possibility of avoiding excessive accumulation of toxic drugs in normal tissue. The slow transport of nanoscale drugs in the tumor after their extravasation from capillaries significantly impedes their delivery to cancer cells. In the absence of convection in the tumor, the transport of nanomedical drugs is determined solely by diffusion, which turns out to be much slower than the diffusion of low-molecular-weight chemotherapeutic drugs. One approach to solving this problem is to develop and apply high-capacity containers with good biodegradability. The choice of the optimal size and shape of submicron particles, as well as the targeted modification of their surface, will significantly increase their adhesion to the vascular and capillary endothelium of primary and metastatic tumors, which are typically characterized by a reduced blood flow. Vaterite CaCO3 particles may be suitable candidates, but the optimization of their loading efficiency is required.
The aim of the study was to obtain CaCO3 submicron particles with the size less than 500nm of various shapes (spherical, ellipsoidal and lamellar) and maximum content of crystallite vaterite phase. Colloidal particles of calcium carbonate were obtained by mass crystallization in aqueous solutions of salts containing calcium ions and carbonate ions. In particular, crystallization of spherical and ellipsoidal vaterite particles was carried out in a mixture of water/glycerin, water/ethylene glycol, water/gelatin1. Samples have been characterized using scanning electron microscopy, X-ray powder diffraction, and porosity measurements. The loading efficiency of photodynamic and chemotherapy drugs (photosens and doxorubicin) have been studied depending on the size, shape and porosity of the particles. For the encapsulation of therapeutic drugs, a number of techniques have been used: adsorption on pre-synthesized porous particles, coprecipitation during the formation of particles, and a new method - adsorption from solution during the freezing of the solvent. To evaluate the effect of the physicochemical characteristics and the rate of dissolution of particles on the release profile of the incorporated substances, the particles were incubated in a model medium at a pH from 4 to 8. The stability of the obtained nanostructured containers and the processes of their recrystallization and dissolution under various external conditions (pH, proteins) have been studied.
This work was performed using the equipment of the Shared Research Center FSRC “Crystallography and Photonics” RAS and was supported by the Russian Ministry of Education and Science” in part of particles characterization. This research was supported by the Russian Science Foundation (Project No. 21-74-10058) in the part of drug loading and release studies.
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