The development of novel excipients for the stabilization of proteins against aggregation
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2011.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2011
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| Online Access: | http://hdl.handle.net/1721.1/62736 |
| _version_ | 1811086617628114944 |
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| author | Schneider, Curtiss P. (Curtiss Paul) |
| author2 | Bernhardt L. Trout. |
| author_facet | Bernhardt L. Trout. Schneider, Curtiss P. (Curtiss Paul) |
| author_sort | Schneider, Curtiss P. (Curtiss Paul) |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2011. |
| first_indexed | 2024-09-23T13:29:06Z |
| format | Thesis |
| id | mit-1721.1/62736 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T13:29:06Z |
| publishDate | 2011 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/627362019-04-11T07:06:22Z The development of novel excipients for the stabilization of proteins against aggregation Schneider, Curtiss P. (Curtiss Paul) Bernhardt L. Trout. 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, 2011. Cataloged from PDF version of thesis. Includes bibliographical references (p. 121-129). Although protein based therapeutics is the fastest growing sector of the pharmaceutical industry, production costs remain incredibly high and rapid commercialization of new protein drug candidates are not being fully realized due to the presence of many barriers, namely the physical and chemical instabilities of proteins. Of these degradation pathways, protein aggregation is arguably the most common and troubling manifestation of protein instability, occurring in almost all phases of development. Protein aggregates are usually nonnative in structure, may exhibit reduced biological activity, and can remain soluble and/or precipitate from solution. In addition to reducing efficacy, if administered to a patient, aggregates can cause adverse reactions, such as immune response, sensitization, or even anaphylactic shock. Therefore, if even a small amount of aggregates form during formulation or storage, a product can be rendered unacceptable. Moreover, for the practical application of traditional and novel drug delivery techniques, protein based therapeutics must be formulated at relatively high concentrations and must remain stable for extended periods of time. The structural differences among various proteins are so significant, that the application of a universal stabilization strategy has not yet been successful, though the effects of common excipients are generally universal. The current approach toward stabilizing protein drugs against aggregation is by trial-and-error testing of different combinations of cosolutes (e.g. salts, sugars, surfactants, amino acids, etc.) using empirically derived heuristics. While ubiquitously used, this approach is inefficient and does not always enable the discovery of stable protein solution formulations. In response to this major problem, we have developed and tested a new class of excipients that has the potential for wide spread application as a universal stabilizer of protein therapeutics. When compared to other commonly used excipients, our novel excipients offer more than an order of magnitude improvement at suppressing the aggregation of a model protein. As a result, if used in formulations, the shelf life of a protein drug, at room or refrigerated temperatures, may be extended from a few weeks to several months or years. Furthermore, these excipients will likely be useful during production and purification for improving yield and lowering downstream purification costs. by Curtiss P. Schneider. Ph.D. 2011-05-09T15:27:46Z 2011-05-09T15:27:46Z 2011 2011 Thesis http://hdl.handle.net/1721.1/62736 717387146 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/1721.1/7582 137 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemical Engineering. Schneider, Curtiss P. (Curtiss Paul) The development of novel excipients for the stabilization of proteins against aggregation |
| title | The development of novel excipients for the stabilization of proteins against aggregation |
| title_full | The development of novel excipients for the stabilization of proteins against aggregation |
| title_fullStr | The development of novel excipients for the stabilization of proteins against aggregation |
| title_full_unstemmed | The development of novel excipients for the stabilization of proteins against aggregation |
| title_short | The development of novel excipients for the stabilization of proteins against aggregation |
| title_sort | development of novel excipients for the stabilization of proteins against aggregation |
| topic | Chemical Engineering. |
| url | http://hdl.handle.net/1721.1/62736 |
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