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.

Background: Drug delivery to the brain tumor is limited due to the presence of the blood-brain barrier (BBB). Objective: This study aims to evaluate the therapeutic effects of cisplatin-loaded PEGylated liposomes, targeted with OX26 antibody (targeted liposomal cisplatin) against transferrin receptor expressing rat glioma C6 cells in vitro environment. Method: The liposomes were synthesized using reverse phase evaporation method and were conjugated to OX26 monoclonal antibody. They were characterized in terms of size, drug encapsulation efficiency, morphology and drug release experiments using dynamic light scattering, atomic absorption spectrometry, scanning electron microscopy, and dialysis membrane methods. Then, their biological activities were evaluated on targeting the BBB. Results: The characterization results showed that spherical nanodrug with the size of 157 nm and drug loading efficiency of 24% were synthesized, which released 64% of the loaded cisplatin after 72 h in a controlled release manner. The nanoparticles caused an increase in the cisplatin cytotoxicity effects by 1.7-, 1.8- and 1.8-fold, compared to cisplatin-loaded PEGylated liposomes (liposomal cisplatin) after 24, 48 and 72h incubation, respectively against C6 cells. Also, targeted liposomal cisplatin showed promising results in the transport of cisplatin across the BBB, in which it caused an increase in the cisplatin cytotoxicity on C6 cells by 2.7- and 2.4-fold, compared to cisplatin and liposomal cisplatin, respectively. Conclusion: Regarding the proper properties of the targeted liposomal cisplatin, it suggests that the potency of the formulation to be evaluated for transport of cisplatin across the BBB and deliver it to brain tumor in vivo environment.