Synthesis and function of bioactive, block copolymer surfactant constructs as relevant to the preparation of anticoagulant and antibacterial medical implant surfaces. Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/js956m31h

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • Nisin, an antibacterial peptide proven to be an effective inhibitor of Gram-positive bacteria, was incorporated into novel block copolymer constructs and tested for retained antibacterial activity. Covalent coupling was achieved by chemical modification of the N-terminal isoleucine to introduce a thiol group. Thiolated nisin derivatives were then linked to poly[ethylene oxide]-poly[propylene oxide]-poly[ethylene oxide] (PEO-PPO-PEO) triblocks that had been end-activated such that terminal hydroxyl groups of the PEO chains were replaced with pyridyl disulfide moieties. The nisin-containing block copolymers were separated from unreacted nisin by dialysis, and showed antimicrobial activity against the Gram positive indicator strain Pediococcus pentosaceus. Antimicrobial activity was determined to be due to a combination of disulfide-linked nisin, and nisin that was not covalently associated with the PEO-PPO-PEO triblocks. While the extent to which nisin retained antimicrobial activity in its disulfide-linked, copolymer form is not clear, reduction of the nisin-containing copolymer constructs with dithiothreitol demonstrated that nisin released from the copolymer constructs did show antimicrobial activity. Thiol groups were also introduced to unfractionated heparin, an anticoagulant glycosaminoglycan, by reaction of carboxyl groups in its iduronic residues with 3, 3’dithiobis (propanoic) hydrazide. Thiolated heparin derivatives were then linked to pyridyl disulfide-activated PEO-PPO-PEO triblocks which had previously been coated onto the surfaces of polystyrene microspheres (1 m diameter). In addition to monitoring the heparin linking reaction spectrophotometrically, the zeta potential of uncoated, triblock-coated, and heparin-containing microsphere suspensions was recorded to provide an indication of the successful surface attachment of heparin. While the surface attachment of heparin in this manner significantly increased the anticoagulant activity of the microsphere suspensions as determined by the Activated Partial Thromboplastin Time (APTT) assay, this result was not fully reproducible due to the random nature of the thiol-modification process, which, after heparin surface attachment, may interfere with heparin function.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Keyword
Subject
Rights Statement
Publisher
Language
File Format
File Extent
  • 1493261 bytes
Replaces
Additional Information
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2007-01-04T19:20:13Z (GMT) No. of bitstreams: 1 Pranav R Joshi_PhD Dissertation.pdf: 1493261 bytes, checksum: b3dd1d2f745dacff907cb5a1a1e1941a (MD5)
  • description.provenance : Submitted by Pranav Joshi (joship@onid.orst.edu) on 2006-12-20T19:10:15Z No. of bitstreams: 1 Pranav R Joshi_PhD Dissertation.pdf: 1493261 bytes, checksum: b3dd1d2f745dacff907cb5a1a1e1941a (MD5)
  • description.provenance : Made available in DSpace on 2007-01-10T18:54:33Z (GMT). No. of bitstreams: 1 Pranav R Joshi_PhD Dissertation.pdf: 1493261 bytes, checksum: b3dd1d2f745dacff907cb5a1a1e1941a (MD5)

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items