Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Pharmaceutical Sciences


Biomedical and Pharmaceutical Sciences

First Advisor

Matthew J. Bertin


New active pharmaceutical ingredients (APIs) continue to be discovered from the natural world. These compounds can be further developed into a range of useful products such as drugs, supplements, or cosmeceuticals. To determine the biological target of the API, the new compounds are evaluated for their biological activity through a combination of in silico, in vitro, and in vivo analyses. These results will determine where the molecular target tissue is located for the API. However, identification of the target is only the beginning of pharmaceutical and cosmeceutical development. A common roadblock in the development of products is the evaluation and manipulation of the permeability of an API through biologically relevant membranes.

Multiple in vitro methods to assess permeability have been developed to predict how APIs will interact with membranes such as the gut, skin, and blood brain barrier (BBB). Utilizing a combination of prediction methods for APIs can allow early indication of drug likelihood, including fundamental permeability factors such as LogP, the measure of lipophilicity. Additionally, the physicochemical properties of the molecule of interest can be evaluated to compare the attributes of the API to other drugs and supplements.

Natural product libraries of varying complexity were evaluated for biological activity followed by permeability analysis and drug likeliness. Samples include crude plant extracts, pre-chromatography fractions from a cyanobacterial bloom, and the pure compounds unnarmicin D and cannabidiol (CBD). Through these workflows, two new anti-inflammatory metabolites have been discovered, a new opioid ligand has been identified, and permeability coefficients for a common cosmeceutical have been evaluated. Early integration of these permeability methodologies will allow better preclinical outcomes for new drug candidates.



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