Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Thesis
Strategies to Enhance Drug Loading and Functionality in Polymeric Ultrasound Contrast Agents
Master of Science (M.S.), Drexel University
01 Sep 2014
DOI:
https://doi.org/10.17918/etd-6146
Abstract
Ultrasound contrast agents (UCA) are currently studied to further improve their diagnostic capabilities and for better targeted delivery of genes and drugs, with a strong focus on cancer therapy. These injectable microbubbles that strongly interact with ultrasound can be loaded with chemotherapeutic drugs, such as hydrophilic Doxorubicin-HCl (Dox-HCl), for successful targeted delivery upon rupturing under focused ultrasound. This reduces the harmful side effects of chemotherapeutic drugs that are administered systemically. Previous studies with UCA made from poly (lactic acid) (PLA) have shown maximum drug loading of 6.2 mg Dox-HCl/ g PLA at an initial loading concentration of 30 mg Dox-HCl/ g PLA. In order to increase the treatment efficiency, Dox loaded magnetic iron oxide nanoparticles (MNP) were encapsulated within the PLA shell. The inclusion of the MNP not only allows for increased Dox loading, but also provides more imaging capabilities, since MNP can be imaged using magnetic resonance imaging (MRI) even after ultrasound-induced rupture of UCA. Preliminary in vitro tests were performed to determine methods of maintaining the highest amount of ultrasound interaction, measured by acoustic enhancement, possible for magnetic nanoparticles capped with oleic acid (MNP-OA) loaded UCA. This was seen at 33wt% MNP-OA loading where the enhancement reached 14.77±0.61 dB. The magnetic nanoparticles had a short shelf life and so, the MNP-OA were further coated with Pluronic acid to form MNP-OA-PA. The hydrophobic Dox (h-Dox), formed after removing the HCl, was loaded onto the MNP, between the oleic acid chains. However, there was a low entrapment of 2.88 [mu]g Dox/ mg MNP. When these MNP-OA-PA were loaded onto the UCA, the resulting UCA were non-echogenic. The problem was identified by loading just the Pluronic acid onto the UCA, which showed that UCA lose their echogenicity when formed in the presence of Pluronic acid. Low loading of Dox onto the MNP-OA together with the decreased acoustic enhancements made the design of Dox-loaded MNP-OA-PA encapsulated in UCA less than was hoped for. After the Dox-HCl was modified to make it more hydrophobic, they were loaded onto PLA UCA to determine whether the drug payload would increase since PLA is also hydrophobic. It was found that in the hydrophobic form, a maximum drug load of 27.18±0.39 mg Dox / g PLA can be achieved upon initial loading of 30 mg Dox / g PLA for the 3wt% h-Dox loading, resulting in a significant increase (p<0.0001) in drug payload when compared to Dox-HCl loading. The highest acoustic enhancement of 12.69±0.81dB was seen at the largest dose recorded (15.3 [mu]g/mL) for the in vitro acoustic enhancement experiment. This increase in drug encapsulation would allow a higher dose of doxorubicin to be delivered to the patient while maintaining the desired acoustic characteristics.
Metrics
34 File views/ downloads
18 Record Views
Details
- Title
- Strategies to Enhance Drug Loading and Functionality in Polymeric Ultrasound Contrast Agents
- Creators
- Mi Thant Mon Soe - 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
- 6146; 991014632325604721