Liposomal delivery of PDE5 inhibitors and UT-15C to human erythrocytes

<p>"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.</p><p>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.</p><p>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 <i>in vivo</i> 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.</p>

Name thesis:degree_name

Ph. D. in Chemistry

Grantor

Missouri University of Science and Technology

Author dc:creator

• Bowles, Elizabeth Anne

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

Repository record dc:identifier

https://scholarsmine.mst.edu/doctoral_dissertations/2529

OAI identifier oai:identifier

oai:scholarsmine.mst.edu:doctoral_dissertations-3534