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


CONCLUSIONS
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.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Szilvia
S
Berkó
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Kálmán F
KF
Szűcs
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; Gedeon Richter Plc., Budapest, Aesthetic Laser and Plastic Surgery, Budapest, Hungary.
Boglárka
B
Balázs
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Erzsébet
E
Csányi
Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary.
Gábor
G
Varju
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Anita
A
Sztojkov-Ivanov
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Mária
M
Budai-Szűcs
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Judit
J
Bóta
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Róbert
R
Gáspár
D000279:Administration, Cutaneous; D061605:Administration, Intravenous; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation; D065569:Gastrointestinal Absorption / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000008:administration & dosage* / Q000097:blood* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009388:Neostigmine
contraction; electroporation; neostigmine; plasma level; smooth muscle; transdermal