Enhancement of Transdermal Delivery of Proteins and Vaccines by Physical Methods---Lasers with Low Fluences and Microdermabrasion

In the last decade, gene delivery and macromolecules are main streams for the basic studies of drug development. However, these drugs are difficult to be administered by oral route because of the biodegradation occurred in the GI tract. Moreover, the patient compliance should be considered when these drugs administered by an injection route. An alternative route for these drugs such as DNAs and vaccines is urgent to solve these problems. Transdermal Drug Delivery System can be utilized as a successful way to substitute the other routes for protein drugs and vaccines. The most important problem that transdermal drug delivery system should be overcome is the barrier property of stratum corneum. Many enhancement methods are developed to conquer this problem, such as permeation enhancers, iontophoresis, electroporation, and sonophoresis. Laser is one of the enhancement methods which is successfully studied in the field of transdermal drug delivery dystem nowadays. The mechanisms of lasers to enhance drug delivery via skin are both the stratum corneum ablation and photomechanical waves to cause ultrastructural alteration. The advantages of lasers are easy operation, precise control of ablation, and fast treatment duration. In this proposal, the effect of lasers on the transdermal delivery of protein drugs and vaccines will be elucidated and developed. Another stratum corneum ablation tool- microdermabration is also utilized in this proposal to compare its enhancing ability to lasers. The proteins with various molecular weights, sequences, and lipophilicities are used to examine the sensitivity of transdermal delivery promoted by lasers. The vaccine models used in this proposal are lysozyme、human carcinoembryonic antigen (CEA) gene、pVR-1216 DNA, and heat-labile enterotoxin. The ELISA titer and immunoglubulins will be determined to examine the immunological responses. A three-year duration is proposed for this study to develop and evaluate the enhancement induced by lasers and microdermabrasion. We cooperate with Department of Dermatology, Taipei Medical University and Department of Dermatology, University of California at San Diego, USA for proteomics investigation. Furthermore, these enhancement methods will be linked to clinical situation for future application.

Project ID:PC9609-3955
External Project ID:NSC96-2628-B182-002-MY3