Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 39). / The endosome-disrupting and pH-responsive poly(2-diethylamino ethyl methacrylate)-core/poly(2- aminoethyl methacrylate)-shell nanoparticles could potentially increase the efficacy of transcutaneous administered vaccines and facilitate the cytosolic delivery of a wide variety of therapeutic macromolecules. One of the goals of this study was to reduce the size of these core-shell nanoparticles to improve their permeation into the skin. Separate nanoparticle syntheses using reduced durations, decreased monomer concentrations, and decreased monomer solubility did not cause a significant decrease in the particle diameter compared to those previously reported. Manipulation of the reaction kinetics did not stabilize smaller particles leaving them susceptible to coagulation. Synthesis of poly(2-diethylamino ethyl methacrylate)/ Poly(ethylene glycol) methacrylate copolymer nanoparticles were sterically stabilized by the amphiphilic polymer brush at the particle surface and exhibited slightly smaller hydrodynamic diameter measured by dynamic light scattering. Manipulation of the reaction kinetics and the monomer ratio could lead to significantly smaller chains. Another goal for this study was to create core-shell nanoparticles with different charged shells to see if the shell could be modified to electrostatically adsorb a wider range of drugs. In addition, the different charges of the shell could affect the nanoparticles' endosome-disrupting abilities and/or their permeation through the skin. / (cont.) Surprisingly, the zeta-potential measurements were the same for each sample though the shells were supposed to have different charges. This suggests that surface charge density of the PDEAEMA core was being measured. When nanoparticles with a smaller PDEAEMA core and a thicker PAEMA shell were synthesized, a change in the zeta potential was observed that was consistent with the larger positive surface charge density and the higher pKb of the PAEMA shell. This suggests that the adsorption of positively charged drugs may be difficult because it would require negatively charged shell that is thick enough to counteract the positive PDEAEMA core. / by Jason S Pellegrino. / S.B.
| Identifer | oai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/57873 |
| Date | January 2008 |
| Creators | Pellegrino, Jason S |
| Contributors | Darrell J. Irvine., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering. |
| Publisher | Massachusetts Institute of Technology |
| Source Sets | M.I.T. Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 39 p., application/pdf |
| Rights | M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission., http://dspace.mit.edu/handle/1721.1/7582 |
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