BME MS Thesis Defense - Michelle Stolzoff

Starts:
3:00 pm on Monday, April 22, 2013
Ends:
5:00 pm on Monday, April 22, 2013
Location:
44 Cummington St, Room 203
Title: "Alteration and Refinement of Cellular Uptake of Expansile Nanoparticles via Tunable Surfactant Formulations"

Committee Members:
Prof. Mark W. Grinstaff (BU/BME, BU/Chemistry, Advisor)
Prof. Joyce Wong (BU/BME)
Prof. Tyrone Porter (BU/ME, BU/BME)

Abstract:
Nanoparticle-based drug delivery has been explored to circumvent the often-toxic chemotherapy treatments used today by providing a more efficient and specific delivery to diseased tissues. Recently we have developed polymeric pH-responsive expansile nanoparticles (eNPs) for intracellular delivery of paclitaxel (Pax) as an improvement upon the traditional methods of delivery of Pax with cremophor. As the eNPs are internalized by the cell, the hydrophobic side chains are hydrolyzed and become hydrophilic, causing the eNPs to slowly swell with water. In this manner, the encapsulation and controlled release of a hydrophobic drug can be achieved. By altering the surface characteristics of the eNPs, one can change the behavior of the delivery vehicle as well as the biological response. To explore this approach, two surfactant strategies were employed. Specifically, the original sodium dodecyl sulfate (SDS) surfactant has been substituted with PEGylated surfactants (either lipids or poloxamers) to improve circulation and in vivo stability. In addition, these surfactants were functionalized to target the folate receptor, which is overexpressed in several cancers. The resulting eNPs retained their swelling characteristics while demonstrating improved cellular uptake in folate receptor-expressing KB and MDA MB 231 carcinoma cells with no change in uptake in the folate receptor non-expressing A549 carcinoma cell line.