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