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2019 07 last edition_LEI XIA.pdf (2.37 MB)

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Study of Zwitterionic Functionalized Materials for Drug Delivery and Protein Therapeutics

Lei, Xia
http://rave.ohiolink.edu/etdc/view?acc_num=akron1555511296878391

Abstract Details

2019, Doctor of Philosophy, University of Akron, Chemical Engineering.
In the study of this Ph.D. dissertation, two research topics related to zwitterionic materials have been investigated. Even though the applications have different objectives, the unique properties that existed in zwitterionic materials have, including charge property and antifouling property, have been used in both of research. The first topic is the development of zwitterionic-peptides gene delivery system. The gene delivery system, with high efficacy, low toxicity, long blood circulation time and targeting the specific cancer cell, is investigated. The second topic is the functionalization of protein therapeutics with zwitterionic polymers. The protein therapeutics with better solubility, stability, and activity is developed. The non-viral gene delivery system is under research due to their low toxicity, low immunogenic and large DNA loading size in gene therapy. Peptides gene delivery system is reported with the cationic charge and buffering effect which overcomes the barrier and delivery DNA into the nucleus. In our group, the economic dextran-peptide hybrid gene delivery system was developed with high transfection efficiency and low toxicity. The first topic of my research was expanded as a continuous work under the same research interest. The effect of the design of peptides length, zwitterionic group and targeting group was studied for the optimization objects on achieving low toxicity, transfection efficiency and blood circulation time, which was summarized into three research projects under this topic. The system was adjusted by the peptides length for toxicity and economic purpose. The system was functionalized with the zwitterionic group for improved stability, enhanced endosomal escape and longer blood circulation time. The system was also conjugating with targeting ligand for targeting gene delivery. It was found that the shorter length of peptides will not provide enough charge to form stable micelle with report DNA. The zwitterionic functionalized material have lower toxicity and lower transfection efficiency compared to non-zwitterionic functionalized dextran-peptides. Moreover, the transfection is considered as high compared to PEI. The micelle stability during pH titration was improved. The folate functionalized zwitterionic gene delivery system did not show any promoted transfection efficiency in this time. Currently, the protein therapeutics are under investigation with their unique treatment effect. There are still many challenges from the development to the application for protein therapeutics. One of the challenges is that the protein desaturates during production and application which will increase the product price and reduce the shelf life and decrease the bioactivity. To solve this problem, the formulation and functionalization are studied. In our group, the functionalization of the protein with zwitterionic chains for better solubility, stability and uninfluenced bioactivity is under study. The second research topic of my work is to functionalize the protein with the zwitterionic group by precise designed peptides chain. With the DNA recombinant technique, the functionalized protein is produced in one pot expression. The protein stability during varies conditions is under investigation. It includes thermostability, pH stability, salt, and urea resistance.
Gang Cheng (Advisor)
Jie Zheng (Advisor)
George Chase (Committee Member)
Lingyun Liu (Committee Member)
Ge Zhang (Committee Member)
Coleen Pugh (Committee Member)
141 p.
Biomedical Engineering; Chemical Engineering; Polymers
Zwitterionic; materials; antifouling; buffer effect; drug delivery system design; gene delivery; protein engineering; protein modification; protein stabilization; dextran; cabolxylbetaine; peptides; AcGFP; IFN beta 1b;

Recommended Citations

Citations

  • Lei, X. (2019). Study of Zwitterionic Functionalized Materials for Drug Delivery and Protein Therapeutics [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1555511296878391

    APA Style (7th edition)

  • Lei, Xia. Study of Zwitterionic Functionalized Materials for Drug Delivery and Protein Therapeutics. 2019. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1555511296878391.

    MLA Style (8th edition)

  • Lei, Xia. "Study of Zwitterionic Functionalized Materials for Drug Delivery and Protein Therapeutics." Doctoral dissertation, University of Akron, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1555511296878391

    Chicago Manual of Style (17th edition)

akron1555511296878391
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© 2019, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.