Ocular Iontophoresis of Nanocarriers for Sustained Drug Delivery to the Eye

<p>Transscleral iontophoresis has been shown as a viable modality to deliver therapeutic drugs for the treatment of eye diseases. Although several studies have been conducted to examine the utility of iontophoresis for both charged and neutral molecules, the understanding of the mechanisms controlling the iontophoretic delivery of macromolecules across human sclera is required to optimize this approach. In addition, transsscleral iontophoresis is limited by fast clearance of the drug from the eye to the systemic circulation, leading to the requirement of repeated iontophoresis administrations. The present dissertation was an effort to understand the significance of flux enhancing mechanisms to optimize transscleral iontophoretic delivery of macromolecules. Another objective of the present dissertation was to develop a sustained release drug delivery system consisted of mixed micellar carriers of phospholipids and surfactants to increase the residence time of drugs in the eye in transscleral iontophoretic delivery.</p><p>Chapter 3 of this dissertation describes the effectiveness of iontophoresis in the delivery of charged macromolecules along with the mechanisms controlling the iontophoretic transport of these macromolecules across human sclera. The results in the transscleral transport study suggested that electroosmosis was the major flux-enhancing mechanism in the iontophoretic transport of macromolecules of low charge to mass ratios such as micellar carriers. However, highly negatively charged macromolecules were more effectively delivered by the direct field effect, electrophoresis. </p><p>The feasibility of transscleral delivery of sustained release drug delivery systems composed of micelles by passive and iontophoretic methods was evaluated using cadaveric human sclera in vitro and the results are described in Chapter 4. The mixed micellar carrier system enhanced the solubility of corticosteroids and effectively transported these corticosteroids across human sclera during cathodal iontophoresis. Drugs were then released in a slow and sustained manner from the carrier system in the sclera after iontophoretic delivery.</p><p>In Chapter 5, the influence of drug lipophilicity on the solubilization potential of a mixed micellar carrier system was determined. In addition, the relationship between drug lipophilicities and drug release profiles of the mixed micellar carrier system was also investigated. The results showed that drug solubility enhancement of the micellar carrier system increased with increasing drug lipophilicities. The more lipophilic drugs displayed slower drug release from the sclera compared with the less lipophilic drugs after iontophoretic drug delivery with the mixed micelles.</p><p>The feasibility of mixed micelles as a sustained release drug delivery system was evaluated in vivo using mouse as an animal model in Chapter 6. Pharmacokinetics study of a corticosteroid in the ocular tissues after transscleral iontophoretic delivery of the mixed micelles was performed. To evaluate the safety of transscleral iontophoresis of the mixed micelles, histological examination of the eye tissues was performed after the mixed micelle and iontophoresis treatments. Histological analysis showed no significant changes in the structure of the ocular tissues treated with the mixed micelles and iontophoresis.</p>

Name thesis:degree_name

PhD

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Pharmacy: Pharmaceutical Sciences/Biopharmaceutics

Grantor dc:publisher

University of Cincinnati

Year dc:date

2012

Author dc:creator

• Chopra, Poonam

Contributors dc:contributor

• Li, Kevin

• Pharmaceuticals
• Ocular drug delivery
• Sustained release
• Mixed micellar nanocarriers
• Transscleral iontophoresis
• Corticosteroids

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353951512

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ucin1353951512