Liposome-encapsulated actin-hemoglobin (LEAcHb) artificial blood substitutes

A new approach to enhance the circulation persistence of liposomes has been applied to develop liposome-encapsulated actin-hemoglobin (LEAcHb) dispersions as potential blood substitutes by introducing an actin matrix into the liposome aqueous core. Asymmetric flow field-flow fractionation coupled with multi-angle static light scattering was used to study the shape, size distribution, and encapsulation efficiency of liposome-encapsulated hemoglobin (LEHb) and LEAcHb dispersions. By polymerizing monomeric actin into filamentous actin inside the liposome aqueous core, LEAcHb particles transformed into a disk-like shape. We studied the effect of an encapsulated actin matrix on the size distribution, hemoglobin (Hb) encapsulation efficiency, oxygen affinity, and methemoglobin (MetHb) level of LEAcHb dispersions, and compared them with plain LEHb dispersions (without actin). LEHb, and LEAcHb dispersions extruded through 400 nm membranes were injected into rats and it was observed that LEAcHb dispersions with 1mg/mL of actin enhanced the circulatory half-life versus LEHb dispersions. The circulatory characteristics of empty PEGylated and non-PEGylated actin-containing liposomes (without Hb) were studied as controls for the LEHb and LEAcHb dispersions in this paper, which displayed maximum circulatory half-lives greater than 72 h. Taken together the results of this study supports our hypothesis that a lipid membrane supported by an underlying actin matrix will extend the circulatory half-life of LEHb dispersions.