Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Chemistry


Chemistry and Biochemistry

First Advisor

Davita L. Watkins

Second Advisor

Jared Delcamp

Third Advisor

Saumen Chakraborty

Relational Format



Polyamidoamine (PAMAM) is a dendrimer structure with a polypeptide backbone architecture. It has been utilized in a wide variety of applications but has found significant utility in biomedical applications. PAMAM has been studied extensively due to its globular structure that is similar to proteins found in the body. The branched architecture and overall size provide a favorable environment for host-guest interactions and allows for the loading of small molecules for therapeutic delivery. Although PAMAM has many benefits for use in the area of therapeutic delivery, a primary area of concern for this molecular architecture is the terminal amines that serve as the end-groups for the branches. At physiological conditions, these terminal amines are protonated resulting in a positive surface charge density on the dendritic structure. These protonated amines are a primary source of toxicity associated with PAMAM dendrimers. Literature shows that too high of a positive surface charge density can lead to various forms of toxicity, such as cell lysis. Specific to PAMAM dendrimers, the size and generation of the dendrimer dramatically affects the ability for this macromolecule to interact with negatively charged biological components leading to myotoxicity or the disruption the secondary structure of proteins.


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