<p>In vivo Glioblastoma Therapy Using Targeted Liposomal Cisplatin</p>

Abstract

Background: Drug delivery systems have demonstrated promising results to cross bloodbrain barrier (BBB) and deliver the loaded therapeutics to the brain tumor. This study aims to utilize the transferrin receptor (TR)-targeted liposomal cisplatin (Cispt) for transporting Cispt across the BBB and deliver Cispt to the brain tumor. Methods: Targeted pegylated liposomal cisplatin (TPL-Cispt) was synthesized using reverse phase evaporation method and thiolated OX26 monoclonal antibody. The formulation was characterized in terms of size, size distribution, zeta potential, drug encapsulation and loading efficiencies, bioactivity, drug release profile, stability and cellular uptake using dynamic light scattering, flame atomic absorption spectroscopy (AAS), ELISA, dialysis membrane, and fluorescence assay. Next, the potency of the formulation to increase the therapeutic effects of Cispt and decrease its toxicity effects was evaluated in the brain tumorbearing rats through measuring the mean survival time (MST), blood factors and histopathological studies. Results: The results showed that TPL-Cispt with a size of 157±8 nm and drug encapsulation efficiency of 24%±1.22 was synthesized, that was biologically active and released Cispt in a slow-controlled manner. The formulation compared to Cispt-loaded PEGylated liposome nanoparticles (PL-Cispt) caused an increase in the cellular uptake by 1.43fold, as well as an increase in the MST of the brain tumor-bearing rats by 1.7-fold compared to the PL-Cispt (P<0.001). TPL-Cispt was potent enough to cause a significant decrease in Cispt toxicity effects (P<0.001). Conclusion: Overall, the results suggest that targeting the Cispt-loaded PEGylated liposome is a promising approach to develop formulation with enhanced efficacy and reduced toxicity for the treatment of brain tumor.

Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin

“…Previous studies prepared a variety of Tf-modified nano-preparations, including liposomes, and reported that the transport efficiency of modified drug-containing liposomes across the BBB was significantly higher compared with that of free drugs, indicating that Tf-liposomes can effectively transport drugs across the brain [ 36 , 37 ]. In the current study, four types of liposomes including Tf-ELE/CTX@BLIP, Tf-ELE/CTX@LIP, ELE/CTX@BLIP and ELE/CTX@LIP were prepared.…”

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

“…Cisplatin is a chemotherapeutic drug used for treating numerous human cancers, such as prostate cancer, ovarian cancer and bladder cancer [ 68 – 70 ]. In recent years, studies have found that Cisplatin has been shown to be effective in combination with other drugs in treating patients with GBM [ 71 – 73 ]. It was inferred that cisplatin might downregulate the expression of HOTAIR.…”

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

“…In recent research, methods to minimize the contribution of the BBB to drug delivery have been explored. These methods include the use of a clinical focused ultrasound device (FUS) and improvement of the delivery system using transferrin-receptor-targeted liposomes [ 46 , 47 , 48 ]. For about 30 years, there have been no alternative drugs for GBM treatment other than TMZ.…”