Synthesis and release characterization of polypeptides for the controlled release of drugs.
dc.contributor.author | Cook, Thomas Joseph | en_US |
dc.contributor.advisor | Amidon, Gordon L. | en_US |
dc.contributor.advisor | Yang, Victor C. M. | en_US |
dc.date.accessioned | 2014-02-24T16:21:29Z | |
dc.date.available | 2014-02-24T16:21:29Z | |
dc.date.issued | 1995 | en_US |
dc.identifier.other | (UMI)AAI9527607 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9527607 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/104448 | |
dc.description.abstract | Polymers of amino acids were studied as potential controlled release devices. The twenty common amino acids have a range of physical-chemical properties, and, through polymerization, they can produce polymers with varying properties. In this dissertation, hydrophobicity was the focus of variability. A sequential polypeptide, poly(Phe-Phe-Gly), and two random copolypeptides, poly(Phe-Phe-Gly)$\sb1$(SerOBzl)$\sb{0.7}$ and poly(Phe-Phe-Gly)$\sb1$(SerOBzl)$\sb{1.2}$, were synthesized using solution phase peptide chemistry techniques. These polymers were studied along with the homopolymers, poly(Gly) and poly(Phe). The hydrophobicity was represented as the average side chain $\pi$ value for an average repeating unit and calculated using the amino acid scale of Fauchere and Pliska or by Hansch substituent values. The $\pi$ values ranged from 0 for poly(Gly) to 1.79 for poly(Phe) based on the Fauchere and Pliska scale and 0 to 2.65 based on the Hansch values. Matrix disks were produced by powder blending a model radiolabeled compound, 17$\alpha$-ethynylestradiol, and the polymer. The release of drug from the disks was studied under in vitro conditions and continued up to 90 days for certain systems. Polymer degradation was not observed under these conditions, however, poly(Gly) disks cracked upon exposure to the release media. Release of the model steroid was strongly dependent on the estimated side chain hydrophobicity. The sole deviant from this series was poly(Gly) which released the drug at a slower than expected rate. Besides the matrix format, poly(Gly) and poly(Phe-Phe-Gly) were formulated into microspheres encapsulating a model protein, FITC-BSA. These particles had a diameter below 1 $\mu$m and the release was compared to similar particles made from poly(scDL-lactic acid-co-glycolic acid). In these studies, the poly(Gly) particles exhibited the fastest release while poly(Phe-Phe-Gly) was the slowest. Microparticle morphology was a key determinant in the release rank. Poly(Gly) formed layered disks; poly(lactic acid-co-glycolic acid) formed smooth spheres; and poly(Phe-Phe-Gly) produced spheres with a rough exterior. These studies support the use of amino acid polymers as controlled release devices. The long in vitro release demonstrates their potential application for long term use. The incorporation and release of a model protein suggests their possible use as vaccine carriers for injectable or oral use. | en_US |
dc.format.extent | 103 p. | en_US |
dc.subject | Chemistry, Pharmaceutical | en_US |
dc.subject | Chemistry, Polymer | en_US |
dc.subject | Health Sciences, Pharmacy | en_US |
dc.title | Synthesis and release characterization of polypeptides for the controlled release of drugs. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Pharmaceutics | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/104448/1/9527607.pdf | |
dc.description.filedescription | Description of 9527607.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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