Doctoral Dissertations

Keywords and Phrases

CGMP; Liposomes; PDE5 Inhibitors; Red Blood Cell; Tadalafil; UT-15C

Abstract

"Previous studies have shown that the controlled release of adenosine triphosphate (ATP) from human erythrocytes is an important mechanism for the regulation of vascular caliber. However, erythrocytes from patients with pulmonary arterial hypertension (PAH) fail to release ATP in response to the physiological stimuli of exposure to low oxygen tension or mechanical deformation of a magnitude these cells would encounter in the pulmonary circulation. This defect could be a significant contributor to the increased pulmonary vascular resistance (PVR) that is the cause of the pathological increase in vascular pressures in humans with PAH.

One important approach to the treatment of PAH is to reduce PVR with the administration of drugs such as prostacyclin or its analogs and phosphodiesterase 5 (PDE5) inhibitors. These medications can be used alone or in combination and may have serious unwanted side effects that are additive when used in combination.

Here an alternative drug delivery technique using drug-loaded liposomes is investigated that may allow for increased drug efficacy and, possibly, reduced unwanted side effects. Liposomes can encapsulate drugs and deliver them directly to specific cells. This research describes the successful incorporation and delivery of a clinically-used PDE5 inhibitor, tadalafil, via liposomes, to human erythrocytes to increase ATP release from erythrocytes exposed to the prostacyclin analog, UT-15C. This demonstrates the effectiveness of this technique and forms the basis for future in vivo trials to improve drug delivery and patient quality of life. Liposomal delivery, currently underutilized clinically, could represent a new treatment paradigm for patients with circulation issues"--Abstract, page iii.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Sprague, Randy S.
Ma, Yinfa
Mormile, Melanie R.
Reddy, Prakash
Wang, Risheng

Department(s)

Chemistry

Degree Name

Ph. D. in Chemistry

Sponsor(s)

United Therapeutics

Publisher

Missouri University of Science and Technology

Publication Date

Fall 2016

Pagination

xi, 44 pages

Note about bibliography

Includes bibliographic references (pages 33-43).

Rights

© 2016 Elizabeth Anne Bowles, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Subject Headings

LiposomesErythrocytesCyclic guanylic acidDrug delivery systems -- Research

Thesis Number

T 11014

Electronic OCLC #

974709854

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Included in

Chemistry Commons

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