Pharmacokinetics, Tissue Distribution and Photodynamic Therapy Efficacy of Liposomal‐Delivered Hypocrellin A, a Potential Photosensitizer for Tumor Therapy

Abstract Hypocrellin A, from Hypocrella bambusae , is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT). Tissue distributions were studied in tumor‐bearing mice as a function of time following administration. The tumor model was S‐180 sarcoma transplanted into one hind leg of male Kunming mice; hypocrellin A (HA) was delivered to the mice by intravenous injection of 5 mg/kg of body weight as a suspension either as a unilamellar liposome or in dimethyl sulfoxide (DMSO)‐solubilized saline. The HA was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was performed by a high‐performance liquid chromatographic technique with detection that utilizes the native fluorescence of HA. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for kidney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in tumor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h post‐injection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the selective accumulation of the dye in tumor with higher maximal levels in tumor and higher ratios of tumor‐to‐muscle and tumor‐to‐skin. Levels of dye were very low or not detectable in the brain. The PDT efficacy of HA in the liposome and DMSO saline systems was determined by evaluating the tumor volume regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the highest retention of HA in tumors. Similarly, the maximal PDT efficacy in DMSO saline was attained at 6 h postinjection, the highest HA retention point in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much higher than that of HA in DMSO saline and even hematoporphyrin mono‐methylether.