Graduation Year

2007

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Edward Turos, Ph.D.

Co-Major Professor

Thomas J. Koob, Ph.D.

Keywords

Burn wound, Infection, Antibiotic, MRSA, Pseudomonas, Wound dressing, Elastin, In vitro, In vivo

Abstract

It has been reported by the American Burn Association that 4,000 people die every year due to burn injury. After survival of the initial trauma, the next major obstacle that must be overcome is combating bacterial infection, the primary cause of mortality for burn victims (Chapter 1). The polyacrylate nanoparticle drug delivery system was created to provide a water-based solution for delivery of highly lipophilic antimicrobials; such as N-thiolated β-lactams, however, with the success of this system for these antimicrobials, it was extended towards other, commercially-available water-soluble antimicrobials through acrylation of the drug monomers, including those with observed bacterial resistance (Chapter 2). Various antibiotics were incorporated into this polyacrylate nanoparticle delivery system by either encapsulation or covalent attachment, and the antibacterial activity was determined in vitro (Chapter 3).

Since current treatment of burn wound infections calls for numerous antimicrobials in order to combat the vast array of microbes that may be present in the wound, a multi-drug conjugated nanoparticle system was constructed and analyzed for antibacterial activity against many pathogens commonly found in burn wounds (Chapter 4). In vitro antibacterial assays suggest that the nanoparticle delivery system rejuvenated the activity of penicillin-based antibiotics against formerly resistant microbes, such as methicillin-resistant Staphylococcus aureus. The multi-drug conjugated nanoparticle emulsion had the added benefit of forming a drug-conjugated polyacrylate polymer film through air-drying and polymer coalescence. Upon topical application to a skin abrasion in a mouse model, a protective barrier was created over the wound.

This film exhibits mechanical properties similar to elastin, a pliant biological material, giving it the elasticity and flexibility required to move and interact with the wound in the same fashion as intact skin (Chapter 5). This film also permits diffusion of essential nutrients and small molecules (such as oxygen and water) required for wound healing. The emulsion was able to be combined with other biological materials, such as collage, to form a biocomposite material expressing the most optimal properties from each constituent (Chapter 6). In vitro cytotoxicity analysis (Chapter 7) and in vivo toxicity studies (Chapter 8) produced positive results indicating that the multi-drug conjugated nanoparticle emulsion is a promising new treatment for the burn wound and other topical skin and soft tissue infections.

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