In vitro evaluation of doxorubicin release from diopside particles on MG-63 and HF spheroids as a 3D model of tumor and healthy tissues

Inna N Bulygina; Saida Sh Karshieva; Elizaveta S Permyakova; Artem A Korol; Evgeny A Kolesnikov; Rajan Choudhary; Fedor S Senatov; Elizaveta V Koudan

doi:10.1016/j.tiv.2024.105830

In vitro evaluation of doxorubicin release from diopside particles on MG-63 and HF spheroids as a 3D model of tumor and healthy tissues

Toxicol In Vitro. 2024 Apr 17:98:105830. doi: 10.1016/j.tiv.2024.105830. Online ahead of print.

Authors

Inna N Bulygina¹, Saida Sh Karshieva², Elizaveta S Permyakova², Artem A Korol², Evgeny A Kolesnikov², Rajan Choudhary³, Fedor S Senatov², Elizaveta V Koudan²

Affiliations

¹ National University of Science and Technology "MISIS", 119049 Moscow, Russia. Electronic address: ibulygina@misis.ru.
² National University of Science and Technology "MISIS", 119049 Moscow, Russia.
³ Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of General Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka St 3, LV-1007 Riga, Latvia; Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Kipsala Street 6A, LV-1048 Riga, Latvia.

PMID: 38641231
DOI: 10.1016/j.tiv.2024.105830

Abstract

Local drug delivery systems based on bioceramics ensure safe and effective treatment of bone defects and anticancer therapy. A promising drug delivery scaffold material for bone treatment applications is diopside (CaMgSi₂O₆) which is bioactive, degradable, and possesses drug-release ability. Currently, in vitro assessment of drug release from biomaterials is performed mostly on a 2D cell monolayer. However, to interpret and integrate biochemical signals, cells need a 3D microenvironment that provides cell-cell and cell-extracellular matrix interactions. In this regard, 3D cell models are gaining popularity. In this work, we proposed the protocol for evaluation of the effect of doxorubicin released from diopside on MG-63 cells and primary human fibroblasts in 3D culture conditions. Tissue spheroids with similar diameters were incubated with doxorubicin-loaded diopside for 72 h, the amount of diopside was calculated in accordance with the required doxorubicin concentration. We demonstrated that doxorubicin is gradually released from diopside and exhibits an activity similar to that of the pure drug at the same total concentration. It is important to note that doxorubicin was more potent on MG-63 spheroids compared to HF spheroids, which confirmed the reliability of spheroids as 3D models of tumor and healthy tissues.

Keywords: Diopside; Doxorubicin; Drug release; Osteosarcoma; Spheroids.