Liposomal delivery of a phosphodiesterase 3 inhibitor rescues low oxygen-induced ATP release from erythrocytes of humans with type 2 diabetes |
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Authors: | Sergey A Dergunov Elizabeth A Bowles Weston Gordon Michael Green August Bierman Mary L Ellsworth Eugene Pinkhassik Randy S Sprague |
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Institution: | 1. Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, Storrs, CT 06269, USA;2. Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA;3. Department of Chemistry, Saint Louis University, 3501 Laclede Avenue, St. Louis, MO 63103, USA |
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Abstract: | ATP release from erythrocytes in response to low oxygen tension requires an increase in cAMP, the level of which is regulated by phosphodiesterase 3 (PDE3). Such release is defective in erythrocytes of humans with type 2 diabetes (DM2). This study tested a hypothesis that direct delivery of the clinically useful PDE3 inhibitor, cilostazol, to erythrocytes of humans with type 2 diabetes using liposomes would restore low-oxygen tension-induced ATP release. Cilostazol was incorporated into liposomes prepared from dimyristoylphosphatidylcholine (DMPC). Liposome-delivery of cilostazol restored ATP release from DM2 erythrocytes to levels which were not different from that released from non-cilostazol treated healthy erythrocytes under the same conditions. There were no observed adverse effects of the liposomes on either healthy or DM2 erythrocytes. The directed liposomal delivery of PDE inhibitors to erythrocytes may help prevent or slow the development of peripheral vascular disease in individuals with DM2 by restoring an important physiological controller of microvascular perfusion while minimizing side effects associated with systemic delivery of some of these inhibitors. |
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Keywords: | Drug delivery Liposomes Erythrocytes Diabetes Phosphodiesterase inhibitors |
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