Biomedical Engineering ETDs

Publication Date

Summer 8-18-2019

Abstract

Regulation of the development, production, marketing, and sales of medical pharmaceuticals and devices in the United States fall under the regulatory functions of the Food and Drug Administration (FDA). The current FDA approval process takes an average of 10 years from start to completion, and costs over $100 million. As a result, companies use many different methods to find additional use of their drugs through marketing directly to the physician, or recycling of previously approved drug moieties. In this work, an evaluation of the in vitro and ex vivo biocompatibility of polymers and drugs in different phases of FDA approval are evaluated. These include polymers and drugs that are 1) being studied for FDA approval (Chapter 3), 2) used for purposes other than their initial clinical setting purposes (Chapter 4 and 5), and 3) deemed safe from studies in the 1960s-1970s and have been used due to their low “toxicity” (Chapter 6). An alternative method of drug delivery is explored to improve the palatability and allow for more precise control of the concentration of drugs delivered for colonoscopy preparations to help alleviate side effects and improve compliance rates is explored in Chapter 7. The cytotoxicity of reagents (NIPAM) used in current experimental protocols prior to FDA approval were investigated as described in Chapter 3. Although other forms of polymerized NIPAM are non-toxic to cells, cpNIPAM purchased from retailers should be purified prior to use to prevent unintended cytotoxic effects. Current surgical procedures often encourage the use of antifibrinolytics to prevent excessive bleeding (Chapter 4), antibiotics, and antiseptics to prevent infection (Chapter 5). This work demonstrated that each of the antibiotics, antiseptics, and antifibrinolytic tested are detrimental to knee joint cells. Chapter 6 showed that PEG 3350 at current therapeutic concentrations changes the behavior of gut cells. Taken together, these chapters emphasize the need for careful evaluation of the possible cytotoxic effects of antibiotics in surgical applications prior to their use. Chapter 7 characterizes the ideal concentrations and their effectiveness as a potential delivery vehicle for PEG 3350 and identifies the optimal fabrication of hydrogels using natural polymers to deliver the maximum amount of drug. Studies were completed evaluating the hydrogels’ pH responsiveness utilizing simple pH solutions as well as simulated gastrointestinal and small intestinal simulation fluids.

Keywords

biocompatibility, cytotoxicity, PEG 3350, pNIPAM, poly(N-isopropyl acrylamide), TXA

Document Type

Dissertation

Degree Name

Biomedical Engineering

Level of Degree

Doctoral

Department Name

Biomedical Engineering

First Committee Member (Chair)

Heather Canavan

Second Committee Member

Eva Chi

Third Committee Member

David Whitten

Fourth Committee Member

Christina Salas

Fifth Committee Member

Steven Walsh

Project Sponsors

Women in STEM award to HEC, MARC to DLC, CTSC to CS, Gates Millenium Scholarship and OGS Excellence to PAN

Available for download on Tuesday, December 14, 2021

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