Ribociclib-loaded folic acid conjugated chitosan-polycaprolactone hybrid nanoparticles for the management of glioblastoma.

The objective of the present research investigation is to assess the anti-glioblastoma potential of Ribociclib (Ribo) and Ribociclib-loaded folic acid conjugated chitosan-polycaprolactone nanoparticles (RFCPNPs). Folic acid was conjugated to glycol chitosan by carbodiimide chemistry, and the formation of the conjugation was confirmed by FT-IR and 1H NMR. RFCPNPs were fabricated by the single emulsification method, and particle size, PDI, surface charge, %EE, and % DL were 127.8 ± 4.37 nm, 0.197 ± 0.012, 5.05 ± 0.1 mV, 70.82 ± 4.25%, and 3.37 ± 0.20%, respectively. The presence of pH-sensitive biological macromolecule, i.e., chitosan, in the carrier system provides pH-sensitivity to RFCPNPs and displays diffusion-controlled release of the Ribo up to 48 h. RFCPNPs exhibited a bi-phasic release pattern, releasing approximately 22.9 ± 3.8%, 23.2 ± 5.8%, and 7.3 ± 1.2% of Ribo within 1 h, and 98.3 ± 1.6%, 86.6 ± 1.5%, and 75.8 ± 5.1% of Ribo were released from RFCPNPs in 48 h in pH 5.5, 6.8, and 7.4 dissolution media, respectively. The half-maximal inhibitory concentration (IC50) of RFCPNPs was found to be 2.7 ± 0.3 and 3.2 ± 0.10 μM in U87 MG and U138 MG cells, which is 8-10-fold-, and 2-3-fold less than the pure Ribo and unconjugated nanoparticles, respectively. The receptor blocking assay demonstrated the significant role of folic acid in the anti-glioblastoma efficacy of the RFCPNPs. RFCPNPs exhibited enhanced ROS generation, apoptosis, and reduced mitochondrial membrane potential of U87 MG cells compared to the pure Ribo. RFCPNPs exhibited approximately 40% apoptotic cells, more than 1.6 times greater than those of the plain drug counterpart. The Ribo and RFCPNPs exhibited 27.1 ± 2.2%, 66.2 ± 1.3% cellular migration inhibition, and 380 ± 46 and 10 ± 4 colonies, respectively. U87 MG spheroids treated with Ribo and RFCPNPs demonstrated 64.3 ± 5.2% and 34.7 ± 11.0% viable cells, respectively. These outcomes suggest that the optimized nanocarrier represents a promising approach for treating glioblastoma.