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Intern: Ashley Sens
Mentor and Faculty Supervisor: Professor Samir Mitragotri
Department: Chemical Engineering |
TRANSDERMAL DRUG DELIVERY (TDD) REPRESENTS A NONINVASIVE AND PAINLESS METHOD OF ADMINISTERING THERAPEUTIC MOLECULES THROUGH THE SKIN
Transdermal drug delivery (TDD)
represents a noninvasive and painless method of administering therapeutic
molecules through the skin. However, in the absence of TDD enhancers, the stratum
corneum is nearly impermeable to large (>300 Da) and/or hydrophilic drug
molecules, such as proteins. The application of low-frequency sonophoresis (LFS)
is an enhancement technique that exponentially improves the delivery of these
molecules transdermally. The mechanisms by which sonophoresis induces greater
skin permeability and increases the flux of drug molecules have only recently
begun to be investigated. This research attempts to partially address these
mechanistic questions as they relate to the microscopic physical alterations
that occur within the stratum corneum. Application of LFS is thought to alter
the stratum corneum by three possible mechanisms: (i) increasing pore radii,
(ii) increasing the number of pores and/or (iii) decreasing the pore tortuousity.
These mechanisms were explored experimentally using full-thickness pig skin
and three model drugs of varying molecular weights: water, mannitol and inulin.
Permeabilities for these drugs were determined as a result of sonophoresis at
an applied frequency of 76 kHz. The steady state permeabilities were calculated
over a 29 hour period. Based on these permabilities and drug concentration the
flux for each model drug was then determined. Finally, the experimentally determined
permeabilities were incorporated into a theoretical model of the transport of
hydrophilic permeants during LFS in order to calculate the pore radii within
the stratum corneum.
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