(542a) Transdermal Protein Delivery Via a Choline-Based Deep Eutectic Solvent | AIChE

(542a) Transdermal Protein Delivery Via a Choline-Based Deep Eutectic Solvent


Ibsen, K. - Presenter, Harvard University
Banerjee, A., Department of Chemical Engineering, University of California Santa Barbara
Mitragotri, S., University of California, Santa Barbara
Iwao, Y., University of Shizuoka
Zakrewsky, M., University of California Santa Barbara

Transdermal Protein Delivery Via A
Choline-based Deep Eutectic Solvent

Presenting Author:  Kelly Ibsen1

Co-Authors:  Amrita Banerjee1, Yasunori Iwao2,
Michael Zakrewsky1, Samir Mitragotri1

1University of California Santa Barbara, USA; 2University of Shizuoka, Japan

outer layer of the skin is a formidable barrier to drug delivery, and many of currently
available methods to increase the permeability of skin, such as chemical penetration
enhancers (CPE) ethanol and Transcutol, also cause irritation and damage. This
research aims to develop low-irritation compounds that enhance transdermal
delivery of proteins. We have shown that CAGE, a benign choline-geranate
eutectic, can deliver small proteins.1 Here, we investigate its
ability to enable macromolecule penetration, using three proteins with a range
of sizes and hydrophobicity: insulin bovine serum albumin (BSA) and ovalbumin
(OVA). Transdermal delivery of macromolecules such as proteins could improve a
myriad of treatments that currently require subcutaneous injections such as
diabetes, where needle phobia results in poor patient compliance and treatment

measure skin penetration compared to standard CPEs, fluorescently-labeled
proteins in 1) CAGE, 2) ethanol, 3) Transcutol®, or 4) buffer were
applied to porcine skin discs in a diffusion cell. Confocal laser imaging was
conducted on skin cross-sections at 24 h.  Insulin and BSA concentrations were quantitatively
measured in the separate skin layers and the acceptor compartment after 24 and
48 h via fluorescence or isotope detection. Additionally, in vivo delivery of insulin was examined by measuring blood glucose
levels in rats after topical application of insulin-CAGE compared to
subcutaneous insulin injection.

laser imaging showed penetration of insulin, BSA and OVA with CAGE into the
skin but not with 50% v/v ethanol, Transcutol or buffer after 24 h. The amount
of insulin or BSA delivered through the skin section at 48 h, as measured by
concentration in the acceptor chamber, was significantly higher with CAGE than buffer.
Topical application of insulin-CAGE on rats resulted in a significant decrease
of 40% in blood glucose compared to insulin in buffer after 4 hours that was
sustained for the length of the 12-hour study, providing a more sustained
effect on blood glucose than subcutaneous injection. These results demonstrate
the effectiveness of CAGE as a potential transdermal delivery vehicle for
therapeutic proteins.

The presenting author is
supported by the National Science Foundation Graduate Research Fellowship under
Grant No. DGE-1144085.


1.     M. Zakrewsky, K. S. Lovejoy, T. L. Kern, T. E. Miller,
V. Le, A. Nagy, A. M. Goumas, R. S. Iyer, R. E. Del Sesto, A. T. Koppisch,
D. T. Fox, S. Mitragotri. Proc. Natl. Acad. Sci. 2014. 111,

2.     D.
Nathan. Diabetes Care. 2014. 37(1): 9-16.