Effect of anionic and cationic n-butylcyanoacrylate nanoparticles on NO and cytokine production in Raw264.7 cells

Abstract

Context: Research on drug delivery carriers that use nanoparticles is currently attracting a great deal of attention. In order to evaluate the safety of these drug carriers for clinical applications, a full assessment of their toxicity and bioactivity is required. Although it is well-known that the surface charge of nanoparticles influences their bioactivity, most of the published studies on n-butylcyanoacrylate (NBCA) nanoparticles as a potential drug delivery carrier are restricted to analyzing the anionic form.

Objective: We compared biological responses of cyanoacrylate anionic nanoparticles with cationic nanoparticles in cultured murine macrophages for assessing cytotoxicity and inflammatory responses.

Materials and methods: The cytotoxicity was evaluated with the MTS and LDH leakage assays. Inflammatory responses were evaluated by measurement of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The interaction of the nanoparticle and the macrophage was assessed by fluorescence microscopy.

Result: Anionic and cationic NP showed no detectable cytotoxicity at a concentration of 10 µg/mL or less. At concentrations greater than 10 µg/mL, cationic NP displayed lower cytotoxicity by comparison with anionic NP. NO, IL-6, and TNF-α production were not induced by anionic or cationic nanoparticles alone. In contrast, both types of nanoparticles decreased NO, IL-6, and TNF-α productions induced by LPS. However, the anti-inflammatory effect of anionic nanoparticles was significantly greater than that of cationic nanoparticles. Nanoparticles were presumed to be either internalized or attached to the cell membranes.

Discussion and conclusion: NBCA nanoparticles are not only important as potential drug carriers but also as promising anti-inflammatory agents that may have therapeutic properties.

Keywords::

• Drug carrier
• polymer
• surface charge
• macrophage
• anti-inflammatory

Acknowledgement

This work was supported by Grants-Aid for Scientific Research (No. 22650237) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Declaration of interest

The authors report no conflict of interest.