Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

Abstract

Purpose

Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats.

Methods

The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography.

Results

Both intravenously and EP-administered neostigmine (0.2–66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes.

Conclusion

The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

Keywords:

• transdermal
• electroporation
• neostigmine
• smooth muscle
• contraction
• plasma level

Acknowledgments

The technical support of Zoltánné Csiszár is highly appreciated. Furthermore, we wish to thank Dr Derm Equipment Ltd. for providing the Mezoforte Duo Mez 120905-D device. Special thanks to Veronika Verseghy for taking photos.

Disclosure

The authors report no conflicts of interest in this work.