Avtor/Urednik		Blagus, Tanja; Markelc, Boštjan; Čemažar, Maja; Kosjek, Tina; Préat, Véronique; Miklavčič, Damijan; Serša, Gregor
Naslov		In vivo real time monitoring system of electroporation mediated control of transdermal and topical drug delivery
Tip		članek
Vol. in št.		Letnik 172, št. 3
Leto izdaje		2013
Obseg		str. 862-871
ISSN		0168-3659 - Journal of controlled release : official journal of the Controlled Release Society
Jezik		eng
Abstrakt		Electroporation (EP) is a physicalmethod for the delivery ofmolecules into cells and tissues, including the skin. Inthis study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes ofelectric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled moleculeswas developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin wasperformedwith new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses rangingfrom 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanatelabeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. Thenew monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantitywas determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery andin a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resultedin enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitudeof 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced withincreasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as apositive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitativelyand quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermaldrug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects asobtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes andwith the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin canbe controlled. Furthermore, the newly developed monitoring systemprovides a tool for rapid real-time determinationof both, transdermal and topical delivery, when the delivered molecule is fluorescent.
Deskriptorji		Skin Cell membrane permability Plasmids Vaccines, DNA Electroporation Blood supply
Proste vsebinske oznake		elektroporacija genska terapija transdermalna aplikacija zdravil electroporation transdermal drug delivery topical drug delivery