Impact of hyaluronic acid molecular weight on silibinin intranasal delivery via hybrid nanoparticle formulation

This study aimed to develop hybrid nanoparticles (LPNs) using hyaluronic acid (HA) of different molecular weights for intranasal delivery of silibinin (SLB) to glioma tumors. LPNs were prepared using low, medium, and high molecular weight HA. Blank LPNs measured approximately 100 nm, whereas SLB-LPNs were about 160 nm. Cryo-TEM confirmed a spherical morphology with an internal multilayer bilayer structure, and the membrane thickness ranged between 8 and 16 nm. Zeta potential was approximately -44.4 mV due to the presence of HA. Isothermal titration calorimetry indicated improved stability and an amorphous structure of SLB within LPNs, particularly when using low molecular weight HA. The drug content and encapsulation efficiency were about 100 % and 60 %, respectively. In vitro, about 85 % of SLB was released over 24 h, significantly higher and prolonged than Free-SLB (only 20 % in 1 h). Cellular uptake in RPMI 2650 cells was increased (about 2-fold) compared to control, while cytotoxicity assays in T98-G glioblastoma cells showed a 50 % reduction in viability after 72 h of treatment with SLB-LPNs. These findings underscore the crucial role of HA molecular weight in optimizing LPNs performance for brain-targeted delivery and highlight their promising potential for intranasal glioma therapy.