Developing a drug delivery vehicle that can control the release kinetics of a therapeutic drug on demand has great potential to improve health by allowing health care professionals to maintain the drug concentration in its therapeutic window and increase the efficiency at which treatment is administered.
On-demand release can be triggered by a range of stimuli including magnetic, radiation, and ultrasound activation. Of the three, ultrasound is the only one indiscriminate of the chemical properties of the material and is the most widely available clinically, which makes it versatile and applicable for many systems. However, existing strategies that use ultrasound as a release stimulus either pop the microcapsules altogether (enabling no subsequent effective control over the kinetics of drug release) or require continuous ultrasonic administration (typically impractical in a clinical setting), both of which are suboptimal. Overcoming at least of these shortcomings would vastly improve on the technology.
In this thesis, microcapsules with a complex shell were fabricated using a modified electrohydrodynamic approach named immersion coaxial electrospraying, which allowed for an increased polymer loading in the shell and improved manipulation of microcapsule size. The complex shell structure of the microcapsules incorporated silica microparticles that acted as corks plugging pores between the inside and outside of the microcapsule. The modified microcapsules were shown to release their payload in the presence of a focused ultrasound signal, while uncorked microcapsules do not release. Release kinetics were shown to be adjustable based on the number of corks initially present in the shell of the microcapsule material.
Altogether, the cork-shell microcapsules fabricated in this thesis show promise as a tunable on-demand drug delivery vehicle that is able to better control release compared to conventional ultrasound triggered microcapsules. / Thesis / Master of Applied Science (MASc) / This thesis focuses on the fabrication of complex microcapsules that can be deliver therapeutic drugs on-demand using ultrasound waves. These microcapsules are composed of a water-based core and a biologically inert shell into which particles are embedded. Upon the application of ultrasound, these embedded particles (like corks on a bottle) are popped out to release the “corks” from the shell, creating pores from which the drug in the microcapsule core can be released. In the absence of ultrasound signals, the microcapsules do not release any of their contents, making these effective for “on-demand” release. These microcapsules are made using a modified process based on electrospraying which allows very precise control over the microcapsules’ physical properties, incorporating a key modification that overcomes an inherent issue with the general technique. These microcapsules also improve on currently used ultrasound triggered drug delivery systems by requiring shorter periods of ultrasound and/or enabling better control over the dynamics of drug release following the ultrasound pulse.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23799 |
| Date | January 2019 |
| Creators | Dorogin, Jonathan |
| Contributors | Hoare, Todd, Biomedical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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