Title

Development of Miriplatin-loaded Nanoparticles against Non-small Cell Lung Cancer

Authors

Zhongyue Yuan, University of the PacificFollow
Zizhao Xu, University of the PacificFollow
Xin Guo, University of the PacificFollow

Lead Author Affiliation

Drug Targeting and Delivery

Lead Author Status

Masters Student

Introduction

Lung cancer claims the highest mortality and the second-most new cases among all oncological diseases. NSCLC accounts for approximately 85% of all newly diagnosed lung cancers. Although platinum-based drugs are standard first-line chemotherapy for stage IIIB/IV NSCLC, accumulating reports have shown the failure of conventional platinum-based regimens due to drug resistance. Miriplatin is a lipophilic anti-cancer drug that has been approved in Japan for transcatheter arterial chemoembolization treatment of hepatocellular carcinoma. Lipid-based nanoparticles such as liposomes, micelles, and solid lipid nanoparticles (SLNs) can encapsulate anti-cancer drugs to improve their water solubility and bioavailability.

Purpose

Lipid-based nano formulations of miriplatin would carry appropriate physiochemical properties to improve the anticancer activity of platinum drugs against NSCLC.

Method

1. Preparation of Formulations: Ultrasmall dots and various SLNs were prepared by film-hydration. The dots were developed with 18:0 PE-PEG2000 and anti-cancer drugs (miriplatin and paclitaxel), while the SLNs were prepared with solid lipids (Trimyristin (TM) and tripalmitin (TP)), 18:0 PE-PEG2000, and anti-cancer drugs.
2. Characterization of Formulations: Sizes and PDI of formulations were measured by Zetasizer. A quantification method of platinum recovery was established using inductively coupled plasma-optical emission spectrometry (ICP-OES). The images by transmission electron microscopy (TEM) displayed the sizes and morphology of formulations.
3. In vitro evaluation of anti-cancer activity against NSCLC: A three-dimensional multicellular spheroid model (3D MCS) of A549-iRFP cells was established. During 7-day treatment, the fluorescent signal was recorded and analyzed by Infrared Imaging System at the 700 nm channel. The cell viability was measured by UV absorbance at 490 nm on microplate reader using the CellTiter 96® AQueous One Solution Cell Proliferation Assay.

Results

1. The dots were smaller (~10 nm) and more homogeneous (PDI~0.2), whereas SLNs of different compositions were much larger (~120 nm) and more heterogeneous (PDI~0.4). For miriplatin-loaded SLNs with different compositions, the sizes decreased (from 177.20 nm to 22.81nm) as the percentage of 18:0 PE-PEG increased (from 5% to 40%).
2. The images by TEM displayed their sizes and morphology that were consistent with the size and PDI measurements by Zetasizer.
3. The quantification of miriplatin by ICP-OES have shown high platinum recovery (>80%) in both ultrasmall dots and SLNs.
4. The ultrasmall dots and selected SLNs showed significantly stronger 3D MCS inhibition against 3D MCS than free miriplatin, and similar anti-cancer activity to cisplatin. Miriplatin-loaded SLNs with more PE-PEG had higher anti-cancer activity.

Significance

The reported lipid-based nanoformulations which carried appropriate physicochemical properties represent a promising delivery system for miriplatin against NSCLC.

Format

Event

Video File

wf_yes