Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2008
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| Online Access: | http://dspace.mit.edu/handle/1721.1/34159 http://hdl.handle.net/1721.1/34159 |
| _version_ | 1811090313067888640 |
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| author | Little, Steven (Steven Ronald) |
| author2 | Robert S. Langer. |
| author_facet | Robert S. Langer. Little, Steven (Steven Ronald) |
| author_sort | Little, Steven (Steven Ronald) |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. |
| first_indexed | 2024-09-23T14:42:08Z |
| format | Thesis |
| id | mit-1721.1/34159 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T14:42:08Z |
| publishDate | 2008 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/341592019-04-11T14:11:44Z Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery Little, Steven (Steven Ronald) Robert S. Langer. Massachusetts Institute of Technology. Dept. of Chemical Engineering. Massachusetts Institute of Technology. Dept. of Chemical Engineering. Chemical Engineering. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. In title on t.p., "beta" appears as lower-case Greek letter. Includes bibliographical references. Genetic vaccination is the administration of nucleic acids to induce cellular expression of antigens, leading to an immune response. Unlike traditional vaccines, this technology has tremendous potential for treating or preventing diseases such as HIV, malaria, and cancer. However, this potential is currently unrealized because of the safety concerns which plague viral vaccine carriers and the inefficiency of nonviral delivery systems when compared to their viral counterparts. A promising and versatile nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect their payload and target it to phagocytic, antigen-presenting immune cells. However, the biomaterial conventionally used in these microparticle formulations, an FDA-approved polyester called poly lactic-co-glycolic acid (PLGA), was not designed specifically to deliver DNA, takes too long to release encapsulated payload, and therefore fails to induce high levels of target gene expression. A new class of novel biomaterials have been synthesized called poly([beta]-amino ester)s which are biodegradable and can have similar physical properties to PLGA, but are pH-sensitive and have gene delivery functionalities. (cont.) Using these materials we can fabricate microparticle-based delivery systems which have relatively high DNA loadings and can significantly buffer the destructive acidic pH microenvironment created by ester bond degradation. These formulations generate an increase of up to 5 orders of magnitude in DNA delivery efficiency when compared to PLGA alone and can be potent stimulators of antigen presenting cells in vitro. We have also demonstrated that incorporating these new biomaterials into microparticulate genetic vaccines can lead to antigen-specific, immune-mediated rejection of a lethal tumor dosage in vivo, a significant advance over conventional formulations. Finally, with the synthesis of libraries containing thousands of structurally diverse PBAEs, it is warranted to develop new methods of fabrication which enable the high-throughput screening of such libraries. Herein, we describe, for the first time, such a rapid fabrication technique and demonstrate that plasmid encapsulated in these formulations is transcriptionally active. by Steven Little. Ph.D. 2008-03-26T20:34:40Z 2008-03-26T20:34:40Z 2005 2005 Thesis http://dspace.mit.edu/handle/1721.1/34159 http://hdl.handle.net/1721.1/34159 69019396 eng 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/1721.1/34159 http://dspace.mit.edu/handle/1721.1/7582 151 leaves application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemical Engineering. Little, Steven (Steven Ronald) Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title | Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title_full | Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title_fullStr | Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title_full_unstemmed | Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title_short | Poly ([beta]-amino ester)s as pH sensitive biomaterials for microparticulate genetic vaccine delivery |
| title_sort | poly beta amino ester s as ph sensitive biomaterials for microparticulate genetic vaccine delivery |
| topic | Chemical Engineering. |
| url | http://dspace.mit.edu/handle/1721.1/34159 http://hdl.handle.net/1721.1/34159 |
| work_keys_str_mv | AT littlestevenstevenronald polybetaaminoestersasphsensitivebiomaterialsformicroparticulategeneticvaccinedelivery |