UVM Theses and Dissertations
Format:
Online
Author:
Chen, Di
Dept./Program:
Materials Science Program
Year:
2010
Degree:
Ph. D.
Abstract:
Sonoporation, enhanced by ultrasound contrast agents has been explored as a promising non-viral technique to achieve gene transfection and targeting drug delivery in recent years. However, the short lifespan of traditional ultrasound contrast agents like Optison® microbubbles under moderate intensity ultrasound exposure limits their application. Liposomes, as drug carriers consisting of curved spherical closed phospholipid bilayer shells, have the following characteristics: 1) The ability to encapsulate and carry hydrophilic or hydrophobic molecules. 2) The biocompatibility with cell membranes. 3) The nanometer size and the relative ease of adding special ligands to their surface to target a specific disease site. 4) The stability in the blood stream. 5) Targeted ultrasound irradiation can induce rupture of liposomes letting the drug encapsulated in them leak out to achieve controlled release of the therapeutic agents at a certain concentration and a delivery rate.
In this thesis, several liposome synthesis methods are presented. Liposomes synthesized in our laboratory were characterized acoustically and optically. Anti rabbit IgG conjugated with Alexafluor 647 was delivered into Jurkat cells in a suspension containing liposomes by 10 % duty cycle ultrasound tonebursts of 2.2 MHz (the in situ spatially averged and temporally averaged intensity, ISATA = 80W/cm2) with an efficiency of 13 %. It has been experimentally shown that liposomes may be an alternative stable agent to Optison® to cause sonoporation. Furthermore, a type of nanometer-sized liposome (<300nm) was synthesized to explore the feasibility of ultrasound-triggered release from drug encapsulated lipsomes. It has been demonstrated encapsulated fluorescence materials (FITC) can be released from liposomes with an average diameter of 210 nm when exposed to high intensity focused ultrasound (HIFU) at 1.142MHz (ISPTA= 900 W/cm2). Rupture of relatively large liposomes (>100nm) and porelike defects in the membrane of small liposomes due to the excitation of HIFU were the main causes of the content release. The great enhancement of HIFU-mediated release in the nanometer-sized liposomes may prove useful for clinical applications.
In this thesis, several liposome synthesis methods are presented. Liposomes synthesized in our laboratory were characterized acoustically and optically. Anti rabbit IgG conjugated with Alexafluor 647 was delivered into Jurkat cells in a suspension containing liposomes by 10 % duty cycle ultrasound tonebursts of 2.2 MHz (the in situ spatially averged and temporally averaged intensity, ISATA = 80W/cm2) with an efficiency of 13 %. It has been experimentally shown that liposomes may be an alternative stable agent to Optison® to cause sonoporation. Furthermore, a type of nanometer-sized liposome (<300nm) was synthesized to explore the feasibility of ultrasound-triggered release from drug encapsulated lipsomes. It has been demonstrated encapsulated fluorescence materials (FITC) can be released from liposomes with an average diameter of 210 nm when exposed to high intensity focused ultrasound (HIFU) at 1.142MHz (ISPTA= 900 W/cm2). Rupture of relatively large liposomes (>100nm) and porelike defects in the membrane of small liposomes due to the excitation of HIFU were the main causes of the content release. The great enhancement of HIFU-mediated release in the nanometer-sized liposomes may prove useful for clinical applications.