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

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.

Automated summary

Loss of cartilage is a common clinical problem. This study focused on using a small molecule called Kartogenin (KGN) embedded in liposomes to protect or repair cartilage. The researchers found that hydrophobically modified chondroitin sulfate (CS) derivatives can interact with the liposome membrane and enhance the chondrogenic properties of the KGN-loaded liposomes. The cytotoxicity of the CS derivatives was reduced when the CS was alkylated, and the higher substituted CS formed stable nanoaggregates on the liposome surface, eliminating the overall cytotoxicity. However, the expression levels of chondrogenic markers were enhanced for the KGN-loaded liposomes coated with lower substituted CS, and the formulation had a decreased hypertrophy effect compared to the pure polymeric derivative.