Graduation Year

2012

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemical Engineering

Major Professor

Susana Lai-Yuen, Ph.D.

Committee Member

Anna Parsons, M.D.

Committee Member

Arun Kumar, Ph.D.

Committee Member

Karl Muffly, Ph.D.

Committee Member

Donald Haynie, Ph.D.

Committee Member

William Lee, Ph.D.

Keywords

Chitosan, Drug delivery, Infectious diseases, Medical device, Microparticles, Uterine sampler

Abstract

Pelvic Inflammatory Disease (PID) is one of the most common causes of morbidity in women. PID is a polymicrobial infection of the female reproductive tract, and is associated with pelvic pain, abnormal uterine bleeding, and tubal damage that can lead to ectopic pregnancies and infertility. It is curable but the effects of PID can be permanent if not properly diagnosed and treated. PID presents as a spectrum of disease and is often missed at early stages; even acute PID can be difficult to diagnose, as there is no single conclusive diagnostic test. Currently, PID is identified and treated syndromically because pelvic pain is the only consistent clinical finding. The Center for Disease Control and Prevention (CDC) recommends doxycycline, a broad-spectrum antibiotic, for treatment but doxycycline can cause gastrointestinal irritation and local inflammation leading to an incomplete treatment. Most cases of PID are polymicrobial infections of the tubes and endometrium, which are not accessible to culture due to the difficulty of procuring samples above the naturally contaminated vagina and distal cervix. Given the difficulty of properly diagnosing PID and the limitations and side effects of the current treatments, there is an urgent need for new approaches for improving the accuracy for diagnosis and treatment of PID. We propose a new and practical approach to collect sterile specimen samples from the endometrium for more accurate PID diagnosis, and to treat the reproductive tract locally using doxycycline-loaded nanoparticles. The proposed research presents a novel sterile uterine sampler cover (SUSC) device that can safely and effectively collect uncontaminated specimen samples from the uterus, and also deliver nano-encapsulated drugs directly to the site of infection. The analysis of uncontaminated endometrium samples is expected to provide an understanding of uterine flora in symptomatic and asymptomatic women, and will lead to the identification of infective microbes in symptomatic women for pathogen-specific treatment. The use of nano-encapsulated doxycycline will enable localized drug delivery to lower drug dosage and minimize side effects for the patient. The doxycycline-loaded nanoparticles are characterized and evaluated based on their drug release properties, size distribution, and tissue response in vitro. This research will lead towards a more effective approach for the diagnosis and treatment of PID while freeing women from prolonged systemic treatments and their adverse effects. Moreover, this research will increase our understanding of the uterine biome under various hormonal and pathologic conditions, in symptomatic and asymptomatic women.

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