Date

8-2016

Document Type

Dissertation

Degree Name

Ph.D.

Department

Department of Biomedical Engineering

Abstract

Well-ordered mesoporous silica has emerged in the past decade as a promising platform in nanomedicine and biomedical applications due to its unique characteristics such as ease of synthesis and surface modification, large surface area and pore volume, controllable pore size and particle size, and bio-compatibility. Synthesis conditions can be adjusted to produce particles with sizes ranging from nanoscale to microscale suitable for diverse applications. Herein, I apply micron-sized particles for targeted delivery of metal chelating ligands in the gastrointestinal tract. Specifically, 20 – 250 micron mesoporous silica functionalized with thiol (SH-SAMMS) was investigated as an orally administered drug for the capture of heavy metals (e.g., mercury, cadmium, and lead) in the gastrointestinal (GI) tract. The three metals have been identified by the World Health Organization (WHO) to be among the top ten chemicals of major public health concern. Dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopropanesulfonic acid (DMPS) were developed decades ago for treating acute, high level toxic metal poisoning. Their use must be closely monitored by medical personnel due to potential renal and liver toxicity, and essential mineral depletion. To date, there is no well-established material to treat chronic, low level heavy metal exposure. I found that SH-SAMMS, given together with the toxic metals or post hoc, reduced dietary methyl mercury and cadmium in organs of rats and helped the rats’ recover from weight loss. It also reduced the blood lead levels of the rats. Due to its non-absorbable nature and high selectivity for the target metals, SH-SAMMS did not alter the essential mineral levels. Thus, data suggest that it has high potential to be used for an extended period of time to treat chronic metal exposure. In another project, I optimize iron-ethylenediamine (Fe-EDA)-SAMMS as a potential phosphate binder. It is aimed for treating hyperphosphatemia, common in end-stage chronic kidney disease and dialysis patients. I improved the Fe deposition method on SAMMS, resulting in a 4-fold increase in binding capacity over the previous report. I also found Fe-EDA-SAMMS to have excellent selectivity for phosphate over other GI tract anions and able to capture phosphate from pH 3 – 11, suitable for GI tract application. Both applications are excellent examples of how nanostructured materials may improve efficacy, safety, and delivery of conventional compounds.

Identifier

doi:10.6083/M4TM796J

School

School of Medicine

Available for download on Monday, November 18, 2019

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