Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination.

Ioanna Theochari,Efthimia Pappou,Aristotelis Xenakis,Harris Pratsinis,Demetris Papahatjis,Vassiliki Papadimitriou,Nikos Assimomytis,Vasiliki Pletsa

doi:10.3390/biomimetics3020013

Abstract

Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensitivity remains a major issue in cancer research. In this context, biocompatible oil-in-water (O/W) microemulsions were developed as matrices for the encapsulation of DPS-2 a benzothiophene analogue, exhibiting high cytotoxicity in various cancer cell lines, among them the MW 164 skin melanoma and Caco-2 human epithelial colorectal adenocarcinoma cell lines. The microemulsion delivery system was structurally characterized by dynamic light scattering (DLS) and electron paramagnetic resonance (EPR) spectroscopy. The effective release of a lipophilic encapsulated compound was evaluated via confocal microscopy. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay. When encapsulated, DPS-2 was as cytotoxic as when dissolved in dimethyl sulfoxide (DMSO). Hence, the oil cores of O/W microemulsions were proven effective biocompatible carriers of lipophilic bioactive molecules in biological assessment experiments. Further investigation through fluorescence-activated cell sorting (FACS) analysis, comet assay, and Western blotting, revealed that DPS-2, although non-genotoxic, induced S phase delay accompanied by cdc25A degradation and a nonapoptotic cell death in both cell lines, which implies that this benzothiophene analogue is a deoxyribonucleic acid (DNA) replication inhibitor.

Highlights

Over the last ten years, research groups worldwide have focused more attention on the development and structural characterization of safe biocompatible, soft nanosized systems to create materials with potential application in the field of targeted drug delivery
Cell proliferation assays were in parallel applied in the non-small cell lung carcinoma cell line A549 (p53wt ) treated under the same conditions and at the same time points; A549 cells were resistant to the cytotoxic effects of DPS-2 and, despite their shorter doubling time (22 h), a marginal (≈10%), nonstatistically significant inhibition of cell proliferation was observed at 72 h (Supplementary Figure S3). These findings indicate the suitability of the proposed O/W microemulsions as carriers. These findings indicate the suitability of the proposed O/W microemulsions as carriers of of the lipophilic compound DPS‐2 into human cell lines
80, triacetin and buffer solution were Pharmaceutically developed as matrices for the encapsulationbased of DPS‐2, a novel benzothiophene analogue

Summary

Introduction

Over the last ten years, research groups worldwide have focused more attention on the development and structural characterization of safe biocompatible, soft nanosized systems to create materials with potential application in the field of targeted drug delivery. Chemotherapy is a type of cancer treatment that uses cytotoxic drugs to kill cancer cells by kills or the their growth of healthy cells, causing important side kills effects. In this respect, targeted stopping or slows slowing growth. Chemotherapy fast-growing cancer cells, delivery of chemotherapeutics using microemulsions could prevent or control side effects and and kills or slows the growth of healthy cells, causing important side effects.

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