Inhalation is an effective means of drug administration for treatment of respiratory diseases. Development of a respirable, stimuli-responsive aerosol formulation would further enhance the drug delivery efficiency. In this thesis, it is postulated that a magnetite/lipid formulation stimulated by alternating magnetic fields can be adapted for use as a thermal-activated delivery system to achieve the desired dose and temporal control of drug release. To test this hypothesis, the following specific aims were carried out: (1) Determine the thermal response of superparamagnetic nanoparticles (SPNs) to alternating magnetic fields, (2) Evaluate the release of solute from temperature sensitive aerosol particles, (3) Assess magnetic-activated release of drug from a lipid matrix, and (4) Study the feasibility of magnetic-activated release of solutes with varying polarity from lipid particles.
SPNs heat production was found to be quantitatively consistent with theory, and incorporation of SPNs into solid lipid matrices allowed magnetic heating. For the second aim, thermal activation was shown to be necessary and sufficient for the release of encapsulated solute using naturally occurring lipids. For the third aim, stimuli sensitive release of a test solute was demonstrated, which coincided with melting of the matrix. As such, "on-off" drug release was shown to be controlled by a magnetic field. The release was diffusion controlled, such that existing transport theory can be used to guide the development of delivery systems with appropriate release characteristics. Finally, solid lipid particles containing test compounds were characterized and assessed in vitro for thermal and magnetic stimuli release. Surface release and particle erosion mechanism were suggested for nanoparticles containing a hydrophobic compound. For the release from microparticles, magnetic activation was observed in microscopic images. Magnetic activated release was detected for core-lipid shell particles containing a hydrophilic solute, which may be a consequence of physical rotation of the SPNs. A quantitative framework was established to judge the feasibility of developing a magnetic-sensitive drug delivery system that is also respirable. In light of this analysis, significant practical challenges were revealed that make this approach impractical with currently available technology.