Add time:08/19/2019         Source:sciencedirect.com

Binding of the photosensitizer etiopurpurin (ET2) to human plasma was assessed, using conditions that would yield a high percentage of ET2 in the form of LDL-bound monomers which may favor photosensitizer tumor localization. Two delivery systems, Cremophor EL (CRM) and dimethyl sulphoxide (DMSO), were used. The binding of ET2 to CRM-modified lipoproteins was compared to the binding of the dye to the native proteins using delivery in DMSO. Plasma-bound monomers and unbound high density aggregates were shown to coexist. The density and rate of formation of the dye aggregates were correlated. The aggregates formed by delivery in DMSO could be partially converted into plasma-bound monomeric ET2. There was no mode-delivery-effect upon the distribution of monomeric ET2 among the plasma proteins. 70% of monomeric ET2 was bound to LDL and most of the remainder to HDL. In delivery in DMSO the yield of LDL-bound dye monomers (up to 30% of added ET2) increased with decreasing concentration of ET2 in the delivery solution and with increasing time of incubation (≤48 hr). Long incubation also induced changes in the densities of LDL and HDL. The yields of LDL-bound monomers (up to 40%) increased with increasing concentration of CRM-bound ET2. High yields of LDL-bound monomers were obtained using both modes of delivery. Although the aggregates associated with the two modes of delivery had different properties. The change in lipoprotein composition might be involved in the conversion of aggregates into plasma-bound monomers.

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