Doctoral Dissertations

Keywords and Phrases

Adsorption; Cellulose Acetate (CA) membrane; Endotoxin removal; Lipopolysaccharide (LPS); Polycaprolactone nanoparticles; Protein purification

Abstract

"Presently, approximately one-third of all biopharmaceutical drugs are derived from biological sources like gram-negative bacteria. Gram-negative bacteria like E.coli are much cheaper to cultivate and provide higher biotherapeutic yield compared to mammalian cells. On extracting the useful biotherapeutics from the gram-negative bacterial cells (E.coli), endotoxin present in the bacteria is released in the surrounding media thus contaminating the lifesaving biotherapeutics. Application of the endotoxin-contaminated therapeutics to humans or animals can cause serious health issues like septic shock, tissue injury and ultimately death. Hence, thorough purification of biotherapeutics before parenteral application is necessary. Although there are multiple methods for removing endotoxins, but achieving high protein recovery and purification efficiency are still a challenge.

We have demonstrated a cost-effective technology using a biocompatible polymer nanoparticle of approximately 800 nm diameter. The polymeric nanoparticle removed > 99% endotoxins from water, phosphate buffer saline (PBS) and protein solutions including monoclonal antibodies (MAb). It also showed a high protein recovery of ~99 %. Additionally, the polymeric nanoparticle was capable of being reused multiple times after being regenerated. Further, to enhance the throughput, flow properties and to scale up the whole system, the polymeric nanoparticles were incorporated in a portable and flat sheet biofilter. The biofilter is effective in removing > 99% endotoxins from water and protein solutions with a protein recovery of > 90%. Finally, the whole filtration set-up being gravity driven minimized cost"--Abstract, page iv.

Advisor(s)

Barua, Sutapa

Committee Member(s)

Barua, Dipak
Liang, Xinhua
Nath, Manashi
Wang, Jee-Ching

Department(s)

Chemical and Biochemical Engineering

Degree Name

Ph. D. in Chemical Engineering

Sponsor(s)

Missouri University of Science and Technology. Technology Acceleration Grant
Missouri University of Science and Technology. Innovation Fund
Missouri University of Science and Technology. Center for Research in Energy and Environment
United States. Environmental Protection Agency

Comments

This work was supported by EPA grant, Technology Acceleration Grant, Missouri S&T’s Innovation Fund, Missouri S&T’s Center for Research in Energy and Environment, and the PI’s start-up funds.

Publisher

Missouri University of Science and Technology

Publication Date

Spring 2020

Journal article titles appearing in thesis/dissertation

  • Polyball: A new adsorbent for the efficient removal of endotoxin from biopharmaceuticals
  • Understanding the mechanism of interaction between endotoxin and polymer nanoparticle

Pagination

xv, 171 pages

Note about bibliography

Includes bibliographic references.

Rights

© 2020 Sidharth Razdan, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Thesis Number

T 11689

Electronic OCLC #

1164805577

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