Formulation, optimization and in vitro cytotoxicity study of Kaempferol-loaded PLGA nanoparticles in glioblastoma multiforme cell line

Abstract

Glioblastoma is one of the most aggressive primary brain tumors, and it is difficult to treat since the blood-brain barrier restricts the transport of many therapeutic medicines to the tumor site. Kaempferol (KMP), a naturally occurring flavonoid, has exhibited promising anticancer action, but its therapeutic applicability is restricted by low bioavailability and water solubility. This study demonstrated systematic Box–Behnken design-based optimization of KMP-loaded poly(lactic-co-glycolic acid)-nanoparticles (PLGA-NPs) and the integrated evaluation of their physicochemical and biological performance against glioblastoma cells. The effect of sonication time, concentration of polyvinyl alcohol (PVA), and PLGA on NP size and entrapment efficiency was assessed. The optimized formulation resulted in NPs of an average particle size of 103.7 ± 2.08 nm, entrapment efficiency of 75.73 ± 0.39%, polydispersity index value of 0.184, and zeta potential of −21.1 mV, showing that the particles were uniform and stable. FE-SEM micrographs showed that the NPs were spherical in shape. FTIR and XRD studies confirmed the incorporation of KMP into the PLGA matrix without undergoing any chemical reaction. In contrast to free KMP, the optimized formulation demonstrated sustained KMP release, enhanced antioxidant activity, greater cytotoxicity toward U87 glioblastoma cells, and comparatively better compatibility with normal L929 fibroblasts, highlighting the potential of PLGA nanoencapsulation to improve the therapeutic performance of KMP. All these results reveal the significant effect of PLGA nanoencapsulation on the physicochemical and biological characteristics of KMP.