Role of cavitation, surfactants, and their synergism in transdermal sonophoresis

The research described in this thesis represents a significant advancement in the current mechanistic understanding of low-frequency ultrasound-mediated transdermal drug delivery. Specifically, while prior research has focused on a more general understanding of the mechanisms associated with low-frequency sonophoresis (LFS), this thesis directly investigates the mechanisms associated with phenomena that occur due to LFS skin treatment. These include a deeper understanding of: i) the reasons for heterogeneous perturbation of skin treated with LFS, ii) the physical mechanism that causes synergism between LFS and chemical penetration enhancers (CPEs), iii) the interactions between traditional and non-traditional surfactants in LFS skin treatments, and iv) the effects of LFS and LFS/CPEs on skin structural perturbation. In the first study of this thesis, the intrinsic properties and formation mechanisms of localized-transport regions (LTRs), and the surrounding less-perturbed non-LTRs, of lowfrequency sonophoresis-treated skin are investigated. By independently analyzing LTR, non- LTR, and total skin samples treated at multiple LFS frequencies, it was found that the pore radii (rpore) within non-LTRs are frequency-independent, ranging from 18.2 - 18.5 A, but significantly larger than rpore of native skin samples (13.6 A). Conversely, rpore within LTRs increases significantly with decreasing frequency from 161 A, to 276 A, and to ao (>300 A) for LFS/SLStreated skin at 60 kHz, 40 kHz, and 20 kHz, respectively. These findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. Therefore, it was proposed that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, while the increased rpore values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of acoustic streaming. Next, the effects of a non-traditional surfactant on LFS treatment were analyzed through a case study with the commonly used fluorescent dye sulforhodamine B (SRB). SRB is often considered to be a purely hydrophilic molecule, having no impact on bulk or interfacial properties of aqueous solutions. However, it was demonstrated that SRB is in fact an amphiphile, with the ability to adsorb at an air/water interface and to incorporate into sodium lauryl sulfate (SLS) micelles. In fact, SRB reduced the surface tension of water by up to 23 mN/m, and the addition of SRB to an aqueous SLS solution was found to induce a significant decrease in the critical micelle concentration (cmc) of SLS. Molecular dynamics revealed that SRB has defined polar "head" and non-polar "tail" regions when adsorbed at the air/water interface as a monomer. These findings have significant implications into LFS-mediated transdermal drug delivery, as the inclusion of SRB into an LFS coupling solution can cause a synergistic increase in skin permeability enhancement. However, in the presence of SLS, SRB actually causes an antagonistic effect due to the resulting change in bulk and interfacial properties.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2011

Author dc:creator

• Polat, Bariș E

Advisor dc:contributor.advisor

• Daniel Blankschtein and Robert Langer.

• 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/1721.1/65764

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/65764