Biodistribution and virus inactivation efficacy of a silicon phthalocyanine in red blood cell concentrates as a function of delivery vehicle.
The silicon phthalocyanine, HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), is a new photosensitizer that can inactivate lipid-enveloped viruses in red blood cell concentrates (RBCC) upon exposure to red light. Because Pc 4 is insoluble in water, it was delivered either as an emulsion in saline and cremophor EL (CRM) or as a solution in dimethyl sulfoxide (DMSO). In RBCC, Pc 4 added in either vehicle distributed between the plasma and red blood cells (RBC) in a ratio of 4:6, similar to the ratio of these components in RBCC 3:7 (i.e. a hematocrit of 70%). Light exposure did not affect this distribution and caused only marginal degradation of Pc 4 at a light dose that inactivates > 5 log10 vesicular stomatitis virus (VSV). Among human plasma proteins, Pc 4 bound mainly (about 70%) to lipoproteins and to a lesser extent to albumin and lower molecular weight proteins when delivered in DMSO. When delivered in CRM, distribution between lipoproteins and albumin became more even. Among the lipoproteins Pc 4 bound almost exclusively to very low-density lipoproteins (VLDL) when delivered in DMSO and to both VLDL and low-density lipoproteins when added in CRM. The rate of VSV inactivation was independent of the delivery vehicle but there was less RBC damage, as measured by hemolysis during storage, when Pc 4 was added in CRM. These results indicate that using CRM as emulsifier can enhance the specificity of Pc 4-induced photochemical decontamination of RBCC for transfusion.
Ben-Hur
E
E
New York Blood Center, NY 10021, USA.
Zuk
M M
MM
Chin
S
S
Banerjee
D
D
Kenney
M E
ME
Horowitz
B
B
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D017646:Organosilicon Compounds / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D011817:Rabbits; D012821:Silanes; D014018:Tissue Distribution; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000254:growth & development
D000998:Antiviral Agents; D007211:Indoles; D017646:Organosilicon Compounds; D014677:Pharmaceutical Vehicles; D017319:Photosensitizing Agents; D012821:Silanes; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon