Breaking the Skin Barrier
Transdermal Drug Delivery without Needles
Professor Samir Mitragotri
Department of Chemical Engineering
University of Santa Barbara
DATE:
Tuesday, November 23, 2004
TIME:
4:00 p.m.
PLACE:
Engineering II Pavilion
ABSTRACT
Transdermal drug delivery offers a non-invasive alternative to hypodermic needles for drug administration. However, skin offers a strong permeation and immunological barrier to drug transport. Accordingly, applications of transdermal drug delivery are limited to only a handful of low-molecular weight lipophilic drugs such as nicotine and estradiol.
We are investigating chemical and physical means of increasing skin permeability to macromolecular drugs in a painless and patient-compliant way. I will present an overview of these methods which include the use of ultrasound, chemical enhancers, and liquid microjets. Ultrasound enhances skin permeability by inducing acoustic cavitation near the skin surface. Shock waves generated from cavitation bubble collapse temporarily disrupt the skin's topmost layer, stratum corneum, and allow the passage of macromolecules such as insulin for the treatment of diabetes, heparin for the treatment of thromboembolism, and vaccines for immunization. Chemical enhancers, which are typically surfactant-like molecules, partition into stratum corneum and enhance its permeability by fluidization of its lipid bilayers or extraction of its lipids. We have developed a high throughput method to screen thousands of chemicals and their combinations for safely and reversibly increasing skin permeability. The leading hits from high throughput screening were found to enhance skin permeability to macromolecules including leuprolide acetate for the treatment of prostate cancer. Finally, liquid microjets offer a needle-free and rapid method of drug administration across the skin. We have developed a pulsatile jet injection method that can deliver drugs across the skin with nanoliter resolution for applications such as patient-controlled analgesia.
Collectively, the above methods make up a versatile toolbox for designing novel transdermal therapies. One or more of these methods can be combined with a drug of choice to achieve painless and needle-free therapy.