Development of Lipid-based Nano Formulations of Miriplatin against Lung Cancer

Loading...

Media is loading
 

Lead Author Affiliation

Pharmaceutical and Chemical Science Program

Lead Author Status

Doctoral Student

Second Author Affiliation

Pharmaceutical and Chemical Science Program

Second Author Status

Masters Student

Third Author Affiliation

Department of Pharmaceutics and Medicinal Chemistry

Third Author Status

Faculty

Introduction

Lung cancer claims the highest mortality and the second most new cases in the US. Cisplatin, the first platinum-based anticancer drug, has the highest potency against lung cancer but carries many severe adverse effects. Miriplatin was discovered with a higher lipophilicity and approved in Japan for the treatment of hepatocellular carcinoma (HCC). Nanocarriers provide a promising platform to overcome the physiochemical barrier of solid tumors and to reduce the toxicity of anticancer drugs.

Purpose

In this study, miriplatin is formulated into various lipid-based nanocarriers (micelles and solid lipid nanoparticles (SLNs)) by a scale-up preparation method to evaluate their anticancer activities against lung cancer.

Method

Miriplatin-loaded nano formulations were prepared by a scale-up method (co-solvent slow evaporation). (Figure 2)

Selected miriplatin-loaded formulations prepared by co-solvent slow evaporation method were characterized by sizes, polydispersity index (PDI), platinum recovery and morphology using transmission electron microscopy (TEM).

A three-dimensional multicellular spheroid (3D MCS) model of A549-iRFP cells was well established for in vitro evaluation of the nano formulations’ anticancer activity against lung cancer. The A549-iRFP 3D MCS were treated by 3-day exposure to miriplatin-loaded nano formulations and 4-day drug-free growth.

Results

Figure 2 shows that the miriplatin-loaded nano formulations (both micelles and SLNs) were successfully prepared by the co-solvent slow evaporation method.

Figure 3 compares the two types of nano formulations, micelles were much smaller (~10 nm in diameter) and more homogeneous (PDI < 0.3), while SLNs were bigger (~ 100 nm in diameter) and more heterogeneous (PDI ~0.8). Both nano formulations showed high platinum recovery (>75%). The TEM images shows that micelles had a morphology of spherical dots at around 10 nm in diameter, while SLNs showed spherical structures with a size distribution from 50 to 150 nm.

Figure 4 highlights that a 3D MCS model of A549-iRFP cells with fluorescent signals was successfully established. Selected miriplatin-loaded nano formulations showed substantial anticancer activity against A549-iRFP 3D MCS, which is comparable to cisplatin, a first line drug against lung cancer. The fluorescent signals indicated that the cancer cells did not relapse after the clearance of the anticancer agents after three-day exposure.

Significance

A co-solvent slow evaporation method has been established as a pharmaceutically viable scale-up method to prepare nano formulations with good reproducibility.

The miriplatin-loaded nano formulations carrying favorable physiochemical properties (smaller size, high platinum drug recovery and round morphological features) could enhance the anticancer activities of platinum drugs against lung cancer.

Format

Event

Video File

wf_yes

This document is currently not available here.

Share

COinS
 

Development of Lipid-based Nano Formulations of Miriplatin against Lung Cancer

Lung cancer claims the highest mortality and the second most new cases in the US. Cisplatin, the first platinum-based anticancer drug, has the highest potency against lung cancer but carries many severe adverse effects. Miriplatin was discovered with a higher lipophilicity and approved in Japan for the treatment of hepatocellular carcinoma (HCC). Nanocarriers provide a promising platform to overcome the physiochemical barrier of solid tumors and to reduce the toxicity of anticancer drugs.