Kartogenin-loaded liposomes coated with alkylated chondroitin sulfate for cartilage repair

Magdalena Wytrwal; Katarzyna Szmajnta; Miroslaw Kucharski; Jakub Nowak; Ewa Oclon; Mariusz Kepczynski

doi:10.1016/j.ijpharm.2023.123436

Kartogenin-loaded liposomes coated with alkylated chondroitin sulfate for cartilage repair

Int J Pharm. 2023 Nov 5:646:123436. doi: 10.1016/j.ijpharm.2023.123436. Epub 2023 Sep 22.

Authors

Magdalena Wytrwal¹, Katarzyna Szmajnta², Miroslaw Kucharski³, Jakub Nowak⁴, Ewa Oclon⁵, Mariusz Kepczynski⁶

Affiliations

¹ Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland. Electronic address: wytrwal@agh.edu.pl.
² Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, al. A. Mickiewicza 30, 30-059 Krakow, Poland.
³ Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, al. A Mickiewicza 24/28, 30-059 Krakow, Poland.
⁴ Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387 Krakow, Poland.
⁵ Laboratory of Recombinant Proteins Production, Centre for Experimental and Innovative Medicine, University of Agriculture in Krakow, 1C Redzina Street, 30-248 Krakow, Poland.
⁶ Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.

PMID: 37742822
DOI: 10.1016/j.ijpharm.2023.123436

Abstract

Cartilage loss is a common clinical problem, which leads to significant pain, dysfunction, and even disability. As a result, there is growing interest in using small, non-protein molecules to protect or repair cartilage. Kartogenin (KGN), a small hydrophobic molecule, shows chondroprotective and chondrogenic properties. In this study, we embedded KGN in liposomes, and the whole system was stabilized by covering it with n-octadecylated (at two different substitution degrees) chondroitin sulfate (CS) derivatives. We investigated the interactions of empty liposomes and KGN-loaded liposomes with both CS derivatives using various physicochemical techniques, which revealed that hydrophobically modified CSs can interact with both neutral lipid membrane and negatively charged loaded-KGN lipid membrane. The cytotoxicity and chondrogenic properties of the polysaccharides and liposome-CS formulations of KGN were analyzed towards mesenchymal stem cells (MSCs). The results showed that the alkylated CS exhibited cytotoxic properties. The higher substituted CS self-assembles into stable nanoaggregates that can form a corona on the surface of liposomes, eliminating the overall cytotoxicity of this polymer. However, all tested chondrogenic markers' expression levels are enhanced for KGN-loaded liposomes and coated by lower substituted CS. Furthermore, the undesirable hypertrophy effect for this formulation significantly decreased compared to pure polymeric derivative.

Keywords: Chondroitin sulfate; Differential scanning calorimetry; Kartogenin; Liposomes; Microscale thermophoresis; Stem cells.