Thesis

Sonophoretic delivery of a model macromolecular drug

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Awarding institution
  • University of Strathclyde
Date of award
  • 2010
Thesis identifier
  • T12708
Qualification Level
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Department, School or Faculty
Abstract
  • The use of low frequency ultrasound as a physical enhancer for transdermal drug delivery is known as sonophoresis. This science is still in its infancy. The aim of this study was to explore how low frequency ultrasound can be used to enhance the transdermal delivery of a model macromolecular drug. Initial studies aimed to validate the output of the ultrasound generator. Hydrophone measurements showed that the actual frequency was very close to the supplier's stated 20kHz value while calorimetric measurements showed that the actual intensities were close to and proportional to that stated by the generator's amplitude dial. Interferon-gamma, with a molecular weight of 17000 Da, was chosen as a model macromolecular drug while transport studies were carried out using full-thickness porcine skins inserted in Franz cells. An ultrasound beam (10% duty cycle) of SATA intensity 3.7 W/cm² was applied for periods not exceeding 5 minutes thus keeping skin surface temperatures from exceeding control levels by more than 3°C. Whereas passive macromolecule flux was virtually zero, 5 minutes sonication allowed about 50 ng/cm² drug to permeate transdermally. Drug transport could be significantly improved by pretreating the skin with sodium lauryl sulphate solution prior to the sonication step. This allowed permeation to reach over 100 ng/cm². However, all other tested chemical enhancers - sodum octyl sulphate, sodium eicosyl sulphate, menthone, carvone, alpha terpineol, oleic acid, linoleic acid and stearic acid did not show such an additive interaction with ultrasound. Interestingly, most of the cumulative permeation profiles were not of the typical lag time followed by linear steady state type. The peculiar effectivity of sodium lauryl sulphate and the irregular permeation profiles require further investigation in order to determine the mechanisms occurring.
Resource Type
DOI
Date Created
  • 2010
Former identifier
  • 820305
Embargo Note
  • The electronic version of this thesis is currently under moratorium due to a licensing issue. If you are the author of this thesis, please contact the Library to resolve this issue.

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