High potency EDC-crosslinked bovine serum albumin nanoencapsulation of berberine enhances in vitro anticancer efficacy against glioblastoma by inducing ROS mediated cell apoptosis

Abstract

Berberine (BER), an isoquinoline plant alkaloid, is known to exhibit anti-tumor properties, but its clinical translation as a drug is restricted due to its hydrophobic nature, quick metabolism, and poor intestinal absorption. Nanoparticles as a drug delivery system provide a potential platform to overcome the aforementioned limitations of these phytochemical-based drugs. Here, we aim to develop EDC-crosslinked bovine serum albumin (BSA) nanoparticles as a drug delivery system for encapsulating berberine (BER) and to further investigate its anti-cancer efficacy against human glioblastoma LN229 cells. Our research demonstrates that the synthesized BSA nanoparticles were spherical in appearance, with an average particle diameter of around 90 nm, as observed under SEM and TEM. The XRD, FTIR, UV-Vis Spectroscopy, and DSC analysis revealed that the crystalline state of BER was transformed into an amorphous state upon encapsulation within the polymeric matrix of nanoparticles. Furthermore, the in vitro cytotoxicity analysis against the LN229 cell line indicated that BER–BSA NPs were more cytotoxic than native BER post 24 hour treatment period. Additionally, the improvement in the cytotoxicity of BER–BSA NPs was supported by enhanced migration inhibition, cellular apoptosis, nuclear condensation, mitochondrial membrane potential loss, and production of highly reactive oxygen species (ROS). To conclude, our work collectively indicates that BSA nanoparticles may serve as an effective platform for improving the anti-tumor activity of berberine against glioblastoma.