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BIODEGRADATION OF ELASTIN-LIKE POLYPEPTIDE NANOPARTICLES
by
Mihir Shah
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(PHARMACEUTICAL SCIENCES)
August 2011
Copyright 2011 Mihir Shah
Object Description
| Title | Biodegradation of elastin-like polypeptide nanoparticles |
| Author | Shah, Mihir Kunjeshkumar |
| Author email | mihirkus@usc.edu;mihir4163@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2011-07-21 |
| Date submitted | 2011-07-21 |
| Date approved | 2011-07-21 |
| Restricted until | 2012-01-21 |
| Date published | 2012-01-21 |
| Advisor (committee chair) | MacKay, Andrew |
| Advisor (committee member) |
Hamm-Alvarez, Sarah Okamoto, Curtis |
| Abstract | Biodegradation has been one of the most important determinants used to ascertain the efficacy of the polymers that are frequently used in drug delivery. The study design of this project focused on a series of the protein polymers derived from the human tropoelastin protein to examine the specific mechanisms of biodegradation. Elastin-like polypeptides (ELPs) are non-immunogenic and biocompatible polymers composed of pentapeptide repeats of Val-Pro-Gly-Xaa-Gly where Xaa can be any amino acid. They undergo inverse phase transition during which they remain in solution below the transition temperature (Tt) but collapse and clump together to form aggregates when heated above their Tt. In this study, ELP mono and di-blocks were treated with proteases like elastase and collagenase below and above their Tt in order to learn if their property of transitioning provided them with a protective advantage over the action of these enzymes. Elastase was significantly able to digest all the ELPs at both the temperatures but collagenase degraded them to a much lesser extent with the exception of V96, which showed a clear difference in sensitivity to the enzymes at below and above its Tt. Also carried out was a study to comprehend the cellular uptake and biodegradation of ELPs in mouse hepatocytes over different time intervals which showed that ELPs are significantly taken up into these cells and internalized and biologically degraded with increase in incubation time. These studies will be of value in understanding the specificity and mechanism of action of different proteases on ELPs. |
| Keyword | biodegradation; cellular uptake; elastin-like polypeptide; hepatocytes; inverse transition cycling; proteases |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Shah, Mihir Kunjeshkumar |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-ShahMihirK-145.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | BIODEGRADATION OF ELASTIN-LIKE POLYPEPTIDE NANOPARTICLES by Mihir Shah A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) August 2011 Copyright 2011 Mihir Shah |
