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PDFOpen Access (License Unspecified), Open Access
Thesis
Formulation, fabrication, and drug loading of PEGylated ultrasound contrast agents
Master of Science (M.S.), Drexel University
Jun 2012
DOI:
https://doi.org/10.17918/etd-3872
Abstract
Previous research has shown that when injected intravenously, drug-loaded polymeric ultrasound contrast agents (UCA) accumulate within the liver and spleen due to recognition by the complement proteins within the blood and uptake by the mononuclear phagocyte system (MPS). The MPS and complement systems are part of the body's natural immune system and should be avoided to allow for proper delivery of drug to the desired site. This study investigates two means of incorporating polyethylene glycol (PEG) into the shell of UCA to facilitate the avoidance mechanisms. PEG is a well-researched molecule used for immune system avoidance. The first route used a PEG-polylactic acid (PLA) copolymer to create the UCA via a water-oil-water emulsion technique. A second approach employed TPGS (d-[alpha] tocopheryl polyethylene glycol 1000 succinate or vitamin E) as a surfactant during the creation of the UCA from pure PLA. The resulting formulations of PEGylated UCA were compared to regular PLA UCA to determine the impact of the addition of PEG on the acoustic, inherent, and drug loading properties of the UCA. In this study, UCA were successfully created using the PEG-PLA copolymer in conjunction with PLA. The optimal PEG-PLA UCA were seen to have an average size less than 3[mu]m, maximal acoustic enhancement over 15dB, a half-life of approximately 10 minutes, and a negative surface charge which was similar to the control. These PEG-PLA UCA did show differences in the surface morphology and the drug loading properties. The PEG-PLA UCA had a collapsed polymer shell which caused a wrinkled surface and may have led to the very low encapsulation of drug (8% encapsulation efficiency). The TPGS UCA successfully produced through this design also had properties similar to the control. These UCA had a maximal acoustic enhancement over 15dB, a half-life around 10 minutes, a negative surface charge, and a smooth surface morphology. However, the size of the TPGS UCA was much more varied than the control, ranging from under 2[mu]m to almost 20[mu]m. The TPGS UCA, similarly to the PEG-PLA UCA, were unable to be successfully loaded with large amounts of drug, having on 2.6% encapsulation efficiency. Both the PEG-PLA UCA and the TPGS UCA showed a statistically significant decrease (P<0.05) in the amount of activated C3a protein compared to the control. This reduction of C3a activity would likely correlate to increased circulation time within the blood stream for these UCA due to avoiding detection of the immune system.
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Details
- Title
- Formulation, fabrication, and drug loading of PEGylated ultrasound contrast agents
- Creators
- James Imre Andorko IV - DU
- Contributors
- Margaret A. Wheatley (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 3872; 991014631958704721