Publication Date

2015

Document Type

Dissertation/Thesis

First Advisor

Gaillard, Elizabeth R.

Degree Name

Ph.D. (Doctor of Philosophy)

Legacy Department

Department of Chemistry and Biochemistry

LCSH

Nanotechnology; Analytical chemistry; Biochemistry; Diabetes--Diagnosis--Research; Eye--Diseases--Treatment--Research; Photochemistry--Research; Drugs--Administration--Research

Abstract

Diabetes mellitus is an endocrinal metabolic disorder characterized by high blood sugar levels which gives rise to complications in various organs of the body. Formation of advanced glycation endproducts is universally considered a biomarker for diabetes. Currently, there are several methods used for the diagnosis of diabetes - A1C, FPG and OGT tests. These methods are based on screening the glycation of hemoglobin. Although, these tests give accurate results in diabetic patients, they have their exceptions. One major disadvantage of measuring blood sugar levels is the hemoglobin turnover, which is faster in case of diabetics and hence is a major disadvantage for diagnosing the patients in their early stages. An early diagnosis would give the patient a chance for intervention by following a diet and exercise regimen to delay the further complications that arise due to diabetes. Therefore, in this work, the biomarkers for diabetes have been investigated and quantified to develop a non-invasive diagnostic tool for diabetes.;Recent studies have shown the effect of AGE formation on the vasculature as well as its potential role in several degenerative diseases. Alpha crystallin is a small heat shock protein found in the lens. It is made of 2 sub-units- &agr;A and &agr;B. While &agr;A is confined to the lens and retina, &agr;B is found ubiquitously in the body. &agr;B sub-units have been shown to express under stress conditions throughout the body. Currently, several research groups are studying the implications of alpha crystallin in diseases like cancer and neurodegenerative diseases. The biochemistry of diabetes, microvascular pathology and neurodegenerative diseases is very similar with respect to formation of AGEs, aggregation and development of hypoxic conditions. Our work dealt with studying the effect of structural changes on the spectroscopic properties of the protein.;Ocular diseases mainly age related macular degeneration (AMD), diabetic retinopathy (DR), cataract and glaucoma are the leading causes of blindness in the world. Ocular drug delivery is a major challenge due to the unique anatomy and physiology of the eye. Ocular barriers can be classified into two types: Static tissue barriers which comprise of different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers; Dynamic barriers which are physiological clearance mechanisms that comprise of tears, choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution. All these barriers cause a decrease in bioavailability of the drug especially to the posterior segment.;Conventional ocular drug delivery through eye drops is complicated due to the barriers mentioned above. About 95% of the drug is washed away by the tears. The next barrier is corneal permeability where the corneal epithelium and the stroma selectively allow the hydrophobic and the hydrophilic drugs respectively to pass through. After bypassing all the barriers, the drug that reaches the target site is about 0.01% of original concentration and is not sufficient for the therapeutic action. As a result, the dose frequency has to be increased. One disadvantage of increasing the dose is that the drug which is washed away by the tears enters into the nasolacrimal gland and passes into the blood stream causing systemic toxicity. Therefore, it is necessary to develop timed/ sustained release drug delivery systems which can efficiently deliver the drugs to the target site without toxicity.

Comments

Advisors: Elizabeth R. Gaillard.||Committee members: Neil B. Blackstone; Barrie P. Bode; Timothy J. Hagen; James R. Horn; Laurence B. Lurio.

Extent

210 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

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