Combination nanochemotherapy of brain tumor using polymeric nanoparticles loaded with doxorubicin and paclitaxel: An in vitro and in vivo study

• Published in: European journal of pharmaceutics and biopharmaceutics 2023-12, Vol.193, p.175-186
• Main Authors: Malekpour, Mohammad Reza, Hosseindoost, Saereh, Madani, Fatemeh, Kamali, Morteza, Khosravani, Masood, Adabi, Mahdi
• Format: Article
• Language: English
• Subjects: Animals; Brain Neoplasms - drug therapy; Cell Line, Tumor; Doxorubicin; Glioblastoma - drug therapy; Glioblastoma - pathology; Lactic Acid; Nanoparticles; Paclitaxel; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2023.11.002

This study aims to overcome physiological barriers and increase the therapeutic index for the treatment of glioblastoma (GBM) tumors by using Paclitaxel (PTX) loaded Poly(lactic co-glycolic acid) nanoparticles (PTX-PLGA-NPs) and Doxorubicin (DOX) loaded Poly (lactic co-glycolic acid) nanoparticles (DOX-PLGA-NPs). The hydrodynamic diameter of nanoparticles (NPs) was characterized by dynamic light scattering (DLS) which was 94 ± 4 nm and 133 ± 6 nm for DOX-PLGA-NPs, and PTX-PLGA-NPs, respectively. The zeta potential for DOX-PLGA-NPs and PTX-PLGA-NPs were -15.2 ± 0.18 mV and -17.3 ± 0.34 mV, respectively. The cytotoxicity of PTX-PLGA-NPs and DOX-PLGA-NPs was augmented compared to DOX and PTX on C GBM cells. The Lactate dehydrogenase (LDH) tests for various formulations were carried out. The results indicated that the amount of released LDH was 262 ± 7.84 U.L at the concentration of 2 mg/mL in the combination therapy, which was much higher than other groups (DOX-PLGA-NPs (210 ± 6.92 U.L ), PTX-PLGA-NPs (201 ± 8.65 U.L ), DOX (110 ± 9.81 U.L ), PTX (95 ± 5.02 U.L ) and PTX + DOX (67 ± 4.89 U.L )). MRI results of the combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs indicated that GBM tumor size decreased considerably compared to the other formulations. Also, combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs demonstrated a longer median survival of more than 80 days compared to PTX (38 days), DOX (37 days) and PTX + DOX (48 days), PTX-NPs (58 days) and DOX-NPs (62 days). The results of locomotion, body weight, rearing and grooming assays indicated that combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs had the most positive effect on the movements of rats compared to the other formulations.