Non-invasive iontophoretic delivery of enzymatically active ribonuclease A (13.6kDa) across intact porcine and human skins

Turning Theory into Practice: The Development of Modern Transdermal Drug Delivery Systems and Future Trends

“…Until recently, the iontophoretic delivery of proteins was not considered to be feasible given their molecular weight and the assumption that electroosmosis was the sole electrotransport mechanism available to these permeants. However, recent reports have demonstrated that iontophoresis can be successfully used for the noninvasive delivery of biologically active proteins into and across the skin - cytochrome c [45], ribonuclease A [46], ribonuclease T1 [47] - a negatively charged 11.1-kDa protein - and human basic fibroblast growth factor [48]. …”

The Pharmaceutical Biochemistry Group: Where Pharmaceutical Chemistry Meets Biology and Drug Delivery

“…migraine [73,74] and chemotherapy-induced emesis [75][76][77] ), therapeutic peptides (triptorelin and vapreotide), [78,79] and conducted mechanistic studies that resulted in the first published reports on the non-invasive transdermal delivery of functional proteins across the skin. [80][81][82][83] Experiments with valaciclovir, a cleavable valine ester prodrug of aciclovir with superior oral bioavailability, showed that its transdermal iontophoresis resulted in several hundred-fold increases in aciclovir delivery due to the charged amino group. [71] Sumatriptan and zolmitriptan are 5HT 1B/1D agonists used in the treatment of acute migraine episodes; their iontophoretic administration was investigated in vitro and in vivo and the results illustrated how the current profile controlled iontophoretic delivery kinetics and, as a result, drug concentrations in the plasma.…”

“…[80] Prior to this report it was generally thought that iontophoresis could only be used with molecules of lower molecular weight (of up to a few kDa). [86] Recently completed studies into the transdermal iontophoresis of ribonuclease A [81] (13.6 kDa), human basic fibroblast growth factor [83] (17.4 kDa) and negatively charged ribonuclease T1 [82] (11.1 kDa) demonstrate that intact, biologically active proteins can be delivered non-invasively across the skin (Fig. 3).…”

Development of antimigraine transdermal delivery systems of pizotifen malate

“…Transdermal diffusion studies are usually carried out at physiological pH 7.4, in which case the solvent flow is from the anode toward the cathode. Some iontophoretic studies have focused on the transdermal penetration of large peptides or proteins, demonstrating that the absorbed protein remains active after current application (Dubey and Kalia, 2010). Both enhancement methods -chemical enhancers and iontophoresis -are reversible and suitable for clinical practice.…”

“…where "JEM" is the contribution of electromigration, "Jtot" is the total flux, and "JEO" is the contribution of the electroosmosis (Dubey and Kalia, 2010;Dubey et al, 2011;Schuetz et al, 2005).…”