Effect of solvents on cutaneous penetration of acridine orange.

The interaction between triheterocyclic dyes (neutral red, proflavine, acridine orange, toluidine blue) and deoxyribonucleic acid is well known (BLAKE and PEACOCK, Biopolymers 6: 1225-1253, 1968; GERSH and JORDAN, J Mol Biol 13: 138-156, 1965; LERMAN, Proc Natl Acad Sci 49: 94-102, 1963) In the presence of fluorescent or incandescent light, these dyes will consistently inactivate herpes virus under the parameters established in the laboratory (HIATT, Trans NY Acad Sci 23: 66-78, 1970; WALLIs, TRULOCK, and MELNICK, J Gen Virol 5: 53-61, 1969). Although clinical application of this phenomenon of photodynamic inactivation for treatment of recurrent herpes simplex infections has been moderately successful (FELBER ET AL, JAMA 216: 835, 1971; FRIEDRICK, Obstet Gynecol 41: 74-77, 1973), clinical factors have not been determined for maximum effectiveness. One of the limiting factors is thle ability of the dye to reach the virus. Partial resolution of this problem has been achieved by the unroofing of viral vesicles before dye application. Theoretically, solvents should help carry the dye through epithelium to the virus and would be of great value when herpetic vesicles are not yet clinically evident. The purpose of this study is to test the effects of water, ethanol, acetone, and dimethylsulfoxide (DMSO) on the cutaneous penetration of acridine orange (AO), a fluorescent triheterocyclic dye with potential clinical use for viral photodynamic inactivation. The backs of six rats were shaved and marked off into quadrants. Quadrants on each of three anesthetized rats were swabbed for one minute with solutions of 1% AO in either water, 50% ethanol, 50% acetone, or 50% DMSO. Quadrants of the other three rats were first scrubbed with one of these solvents for one minute and then swabbed for one minute with 1% AO in water. Skin biopsy specimens were immediately frozen and sectioned in a cryostat for fluorescent microscopy. Prescrubbing the skin with ethanol or acetone resulted in total epithelial fluorescence whereas all others produced only patchy superficial staining (Table).