Photochemical decontamination of red blood cell concentrates with the silicon phthalocyanine PC 4 and red light.
Various approaches are being developed for virus inactivation of red blood cell concentrates (RBCC) in order to increase the safety of the blood supply. We have been studying the silicon phthalocyanine Pc 4 for this purpose, a photosensitizer activated with red light. Pc 4 targets the envelope of pathogenic viruses such as HIV. To protect RBC during the process two main approaches are used: (i) inclusion of quenchers of reactive oxygen species produced during the treatment. Tocopherol succinate was found to be most effective for this purpose; (ii) formulation of Pc 4, a lipophilic compound, in liposomes that reduce its binding to RBC but not to viruses. As a light source we used a light emitting diode array emitting at 670-680 nm. An efficient mixing device ensures homogenous light exposure during treatment of intact RBCC. Treatment of 50 ml RBCC with 5 microM Pc 4 and 18 J/cm(2) light results in the inactivation of > or = 5.5 log(10) HIV, > or = 6.3 log(10), VSV and > or = 5 log(10) of PRV and BVDV. The relative sensitivities of these viruses based on the slope of virus kill versus light dose are 1.0, 1.25, 1.5 and 1.9 for HIV, VSV, PRV and BVDV, respectively. To achieve the same level of virus inactivation in 350 ml RBCC, the light dose needed is 40 J/cm(2). HIV actively replicating in CEM cells is as sensitive as cell-free and HIV in latently infected cells is 3-4 times more sensitive. Parasites that can be transmitted by blood transfusion (P. falciparum and T. cruzi) are even more sensitive than viruses. Following treatment, RBCC can be stored for 28 days at 4 degrees C with haemolysis below 1%. Previous studies under less favourable conditions showed that baboon RBC circulated with an acceptable 24 hr recovery and half-life. Genetic toxicological studies of Pc 4 with or without light exposure (mutagenicity in bacteria, mammalian cells in vitro and clastogenicity in vivo) were negative. We conclude that a process using Pc 4 and red light can potentially reduce the risk of transmitting pathogens in RBCC.
Ben-Hur
E
E
V.I. Technologies, Inc. (Vitex), New York, NY 10032, USA.
Chan
W S
WS
Yim
Z
Z
Zuk
M M
MM
Dayal
V
V
Roth
N
N
Heldman
E
E
Lazo
A
A
Valeri
C R
CR
Horowitz
B
B
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001688:Biological Products / Q000592:standards*; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects*; D004340:Drug Contamination / Q000517:prevention & control*; D004912:Erythrocytes / Q000821:virology*; D006678:HIV / Q000187:drug effects*; D011558:Herpesvirus 1, Suid / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008027:Light; D017646:Organosilicon Compounds / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011817:Rabbits; D012821:Silanes; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D000998:Antiviral Agents; D001688:Biological Products; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D012821:Silanes; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon