Elucidation of chemically-induced transdermal transport processes

In this thesis, chemically-induced transdermal transport enhancement has been examined as one of the many techniques currently used to increase the skin permeability to a broader range of pharmaceutically relevant drugs. By taking advantage of the current developments in instrumentation technology, the mechanisms underlying the well-known chemical enhancer action of oleic acid have been examined using novel applications of Two-Photon Microscopy (TPM). For the first time, TPM was used to visualize and quantify the oleic acid-induced three-dimensional spatial distributions of rhodamine B hexyl ester (RBHE), a model hydrophobic fluorescent probe, and of sulforhodamine B (SRB), a model hydrophilic fluorescent probe, based on a sampling of 4 to 6 different skin sites per skin sample. The fluorescent probe intensity profiles, that capture the fluorescent probe concentrations as a function of skin depth, were further evaluated using fundamental transport equations to quantify the oleic acid-induced changes in the vehicle to skin partition coefficient, the concentration gradient, the skin diffusion coefficient, and the skin barrier diffusion length. The application of the quantification methodology revealed that oleic acid-induced increases in the probe vehicle to skin partitioning was the primary effect for both the hydrophobic and the hydrophilic model fluorescent probes. The validity of the transport property enhancement values calculated based on the sample sizes examined (4-6 skin sites), was then addressed, in light of the inherent heterogeneity of the skin morphology.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Yu, Betty (Betty Pei Yuan), 1974-

Advisor dc:contributor.advisor

• Daniel Blankschtein.

• Chemical Engineering

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8494

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8494