Liposomal delivery of a phosphodiesterase 3 inhibitor rescues low oxygen-induced ATP release from erythrocytes of humans with type 2 diabetes

• Liposomes can deliver phosphodiesterase (PDE) inhibitors to erythrocytes.
• No adverse effect of drug-loaded liposomes on erythrocytes was observed.
• Release of ATP from erythrocytes of patients with type 2 diabetes was investigated.
• Liposome-delivered PDE inhibitors restore the release of ATP in response to low O2.

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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