Evaluation of nanoencapsulated verteporfin's cytotoxicity using a microfluidic system

J Pharm Biomed Anal. 2016 Aug 5:127:39-48. doi: 10.1016/j.jpba.2016.02.052. Epub 2016 Mar 5.

Abstract

A new-generation of nanoencapsulated photosensitizers could be a good solution to perform effective photodynamic therapy (PDT). In this paper, we present physicochemical characterization and cellular investigation of newly prepared long-sustained release oil-core polyelectrolyte nanocarriers loaded with verteporfin (nano VP) in relation to free VP. For this purpose, a macroscale multiwell plates and multifunctional microfluidic system (for three types of cell cultures: monoculture, coculture and mixed culture) were used. A physical analysis of nano VP showed its high stability, monodispersity with unimodal shape and highly positive charge, what made them good candidates for cancer treatment. Biological properties (cellular internalization and uptake as well as cytotoxicity) of nano and free VP were evaluated using both carcinoma (A549) and normal (MRC-5) human lung cells. It was investigated that verteporfin was accumulated in cancer cells preferentially. Low cytotoxicity of the tested photosensitizer was observed in both macro, and microscale. However, in experiments performed in the microsystem, nano VP allowed the reduction of cytotoxic effect, especially in relation to the normal cells. It could result from the specific environment of cell growth in the microsystem which can quite closely mimic the in vivo conditions. Our results suggest that the presented microsystem could be a very useful microtool for testing of new generation of photosensitizers in various configurations of cell cultures, which are difficult to perform in the macroscale. Moreover, the prepared nano VP could be successfully used for further research i.e. evaluation of PDT procedures.

Keywords: Cytotoxicity; Lab-on-a-chip; Nanoencapsulated photosensitizers; Photodynamic therapy; Verteporfin.

MeSH terms

  • A549 Cells
  • Cell Survival / drug effects
  • Drug Compounding
  • Humans
  • Lab-On-A-Chip Devices*
  • Lung / cytology
  • Lung / drug effects
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods*
  • Nanostructures / chemistry*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / toxicity
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Porphyrins / toxicity
  • Verteporfin

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin