Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.

Tamás Horváth,Mária Deli,Piroska Szabó-Révész,Alexandra Bocsik,Szilvia Veszelka,Rita Ambrus,Csilla Bartos,Gabriella Újhelyi,Lóránd Kiss

doi:10.3390/molecules21050658

Abstract

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations.

Highlights

Interest in intranasal administration as a non-invasive route for drug delivery continues to grow rapidly
The high vascularization of the nasal mucosa affords a rapid onset of therapeutic effect and it can be administered by the patient or a physician
Drugs can cross through the nasal mucosal membrane using two different pathways: transcellularly—across the cell—and paracellular, via the intercellular tight junctions

Summary

Introduction

Interest in intranasal administration as a non-invasive route for drug delivery continues to grow rapidly. Nasal delivery requires special formulations and vehicles [2,3] to achieve the right bioavability. Excipients, such as absorption enhancers or mucoadhesive polymers, can increase the drug residence time in the nasal cavity and enhance the absorption [4,5]. Because of the Molecules 2016, 21, 658; doi:10.3390/molecules21050658 www.mdpi.com/journal/molecules sensitiveness of the thehave active ingredients but the additives are needed adequate models for respiratory real toxicitymucosa, data [6]. Our groups recently optimized a human nasal epithelial to be tested in adequate models for real toxicity data [6]

Objectives

Discussion

Conclusion