Although great progress has been made, cancer still remains one of the most prevalent maladies plaguing mankind. New treatment methodologies using nanoparticles have come to the forefront by allowing for enhanced delivery of therapeutics to the tumor site. The design of the nanoparticle should allow for long circulation times, tumor-specific targeting and efficient release at the site of action. This requires that both the external shell and internal core of the nanoparticle be carefully selected to meet the maximal criteria of each of these steps. Poly(sialic acid) (PSA), a naturally occurring polysaccharide, meets all of the benchmarks of an effective exterior coating yet remains relatively unexplored in the field of drug delivery. Due to stealth properties, natural tumor targeting ability, and inherent pH-responsive elements, PSA has frequently been viewed as a “next-generation” surface coating. Just as important, the internal composition of the carrier should aid in effective drug loading but also rapid release. The selection of the core containing groups as well as therapeutic should be maximized in order to customize the carrier to drug. Here, we have developed PSA micelles composed of various internal groups selected to maximize drug loading and facilitate release. Loading of the chemotherapeutic doxorubicin was optimized through variations in non-covalent bonding forces between drug and carrier. Furthermore, PSA micelles composed of internal pH-responsive groups of varying hydrophobicity were also developed to tailor micelle swelling points at conditions analogous towards those found upon cellular uptake. Both of these were effective delivery platforms towards MCF-7 human breast adenocarcinoma cells. / Bioengineering
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/2122 |
| Date | January 2018 |
| Creators | Pawlish, Gerald Joseph |
| Contributors | Lelkes, Peter I., Comolli, Noelle K., Gligorijevic, Bojana, Har-el, Yah-el, Huang, Zuyi |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 249 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/2104, Theses and Dissertations |
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