4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery

Background

Cisplatin has proved itself an effective therapeutic approach in a variety of solid tumors. However, its therapeutic concentration was limited since the presence of variant inevitable side effects. Nanoparticles (NPs) developed from amphiphilic copolymers have drawn great attention for prolonging drug residency in blood circulation, increasing tumor accumulation, reducing serum protein adherence and preventing uptake by the reticuloendothelial system (RES). Previously, we synthesized polyethylene glycol (PEG)- polycaprolactone (PCL) NPs as anticancer drug and had confirmed its efficacy in vitro. To comprehensively study the influences of cisplatin-loaded PEG-PCL copolymeric NPs, we enlarge the amount of murine models and applied more physical tests to offer a broader view of the impact that cisplatin-loaded PEG-PCL copolymeric NPs brought about.

Methods

We observed the physical alteration of hepatoma-bearing mice and the tumors after administration of cisplatin-loaded PEG-PCL nanoparticles (NPs). Cell uptake and apoptotic rates were measured through fluorescence microscopy and flowcytometry. Murine blood was collected and examined. Positron emission tomography/computed tomography (PET/CT) was utilized for the detection of tumor metabolic status.

Results

The biopsy and the measurement of tumor volume and murine weights have confirmed the therapeutic efficacy of cisplatin-loaded NPs and was positively related to the dosage of cisplatin. Fluorescence microscope images indicated a better cellular uptake rate of cisplatin-loaded NPs with intracellularly-aggregated, heterogeneous rhodamine B observed in LoVo cells. A decline of apoptotic rates in cisplatin-loaded NPs was measured. Blood tests exhibited less side effects in cisplatin-loaded NPs with higher level of white blood cells and lower aspartate transaminase (AST). PET/CT images revealed less intensity of FDG uptake in murine received higher dosage of cisplatin-loaded NPs.

Conclusions

Nanoparticles prepared from PEG-PCL/PCL hybrids could be a promising drug carrier for intratumoral delivery with greater efficacy and less side effects. This study provides a theoretical basis for possible clinical application.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Comprehensive Cancer Center of Drum-Tower Hospital Comprehensive Cancer Center of Drum-Tower Hospital Comprehensive Cancer Center of Drum-Tower Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.