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Effect of Delivery System on the Pharmacokinetics and Tissue Distribution of bis (Di‐lsobutyl Octadecylsiloxy)Silicon 2,3‐Naphthalocyanine ( iso BOSINC), a Photosensitizer for Tumor Therapy
Author(s) -
Zuk Maria M.,
Rihter Boris D.,
Kenney Malcolm E.,
Rodgers Michael A. J.,
KreimerBirnbaum Martha
Publication year - 1996
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1996.tb03004.x
Subject(s) - photosensitizer , photodynamic therapy , chemistry , pharmacokinetics , saline , methylene blue , distribution (mathematics) , spleen , polyethylene glycol , chromatography , pharmacology , biochemistry , medicine , photochemistry , endocrinology , photocatalysis , mathematics , organic chemistry , catalysis , mathematical analysis
— Bis (di‐isobutyl octadecylsiloxy)silicon 2,3‐naphthalocy‐anine ( iso BOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for photodynamic therapy (PDT). Tissue distributions were studied in tumor‐bearing rats as a function of delivery system and time following administration. The tumor model was an N ‐(4‐[5‐nitro‐2‐furyl]‐2‐thiazolyl) formamide (FANFT)‐induced urothelial cell carcinoma transplanted into one hind leg of male Fischer 344 rats; iso BOSINC was delivered to the rats by intravenous injection of 0.50 mg/kg of body weight as a suspension either in 10% Tween 80 in saline (Tween) or 10% (Cremophor® EL + propylene glycol) in saline (Cremophor). The iso BOSINC was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was by a high‐performance liquid chromatographic technique with detection that utilizes the native fluorescence of the naphthalocyanine derivative. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for spleen and liver. The iso BOSINC retention in tumors was high and was vehicle dependent. For Tween, the maximal ratio of dye in tumor versus peritumoral muscle occurred 12 h after injection; for Cremophor, the maximal ratio occurred later, 336 h postinjection. When the drug was delivered in Tween, iso BOSINC in serum showed two compartment kinetics: half‐lives of about 2 and 11 h were found for the distribution and the elimination phases, respectively. When Cremophor was the vehicle, the elimination half‐life was about 20 h, and one compartment kinetics was observed. The latter findings may explain the generally higher levels of the dye attained by the tissues at later times with Cremophor as the vehicle. An interesting exception wasthat after 7 and 14 days postinjection in Tween, the levels of dye found in testes were six‐ to seven‐fold higher than those found after Cremophor delivery. Levels of dye were very low or not detectable in the brain. Optimal parameters for PDT of tumors with this novel photosensitizer are clearly time‐ and vehicle‐dependent, and future PDT studies will need to incorporate these modulators.