Advancing Glioblastoma Treatment: Aptamer-Mediated, Long-Circulating, Cationic, PEGylated Hybrid Liposomes with Bavachalcone

<b>Background:</b> Glioblastoma, a formidable brain tumor, poses a significant therapeutic challenge. Current treatments face limitations due to the infiltrative nature and resistance of glioblastoma cells.<br/><b>Aim:</b> To explore the brain-targeting efficacy of cationic, long-circulating, targeting PEGylated liposomes incorporating transferrin, folate vitamins, and cationic albumin as aptamers (hybrid-liposomes). These liposomes are entrapped with poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing the anticancer ligand Bavachalcone (BCN), with the goal of advancing therapeutic strategies for glioblastoma.<br/><b>Materials and Methods:</b> PLGA nanoparticles were formulated to encapsulate Bavachalcone. Characterization involved TEM, FE-SEM, FT-IR, XRD, particle size, and zeta potential analysis, confirming successful formulation. Liposomes were prepared via the ethanol-injection method and characterized using a particle size analyzer, zeta potential, TEM, and CSM. In silico studies encompassed network pharmacology, docking, and simulation for efficacy assessment. In vitro cell line studies utilized U87MG, LN-229, and T98G to evaluate cytotoxic effects.<br/><b>Results:</b> In silico studies unveiled the potential inhibitory effects of BCN on glioblastoma growth. Prepared NPs exhibited a particle size of 187 ± 0.5 nm, zeta potential of -33 mV, and drug entrapment efficiency of 89.33 ± 0.5%. Liposomes displayed a favorable particle size of 175.5 ± 0.29 nm with a positive surface charge of 8.72 ± 0.53 mV. Encapsulation efficacy was measured at 77.8 ± 0.61% for BCN. In vitro drug release studies demonstrated significantly higher cumulative release rates of BCN over 82 h. Hybrid liposomes exhibited superior cytotoxicity and accelerated apoptosis in glioblastoma cell lines (U87MG, LN-229, and T98G) through MTT assays. Cellular uptake studies confirmed enhanced internalization in glioblastoma cells. Cell viability assays demonstrated improved cytotoxic effects on glioblastoma cells.<br/><b>Conclusion:</b> Bavachalcone exhibited promise against glioblastoma, supported by in silico and in vitro studies. Hybrid liposomes offer an innovative approach for enhanced drug delivery, addressing BBB challenges. This approach sheds light on the potential of natural compounds and nanotechnology for enhanced glioblastoma treatment.