Pharmacokinetics, tissue distribution and photodynamic therapy efficacy ofliposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy

Hypocrellin A, from Hypocrella bambusae, is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT), Tissue distri butions were studied in tumor-bearing mice as a function of time following administration. The tumor model was S-180 sarcoma transplanted into one hin d 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-performa nce liquid chromatographic technique with detection that utilizes the nativ e fluorescence of HA. Independent of the delivery system, the dye was retai ned in tumors at higher concentrations than in normal tissues, except for k idney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in t umor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h postinjection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the s elective accumulation of the dye in tumor with higher maximal levels in tum or and higher ratios of tumor-to-muscle and tumor-to-skin, Levels of dye we re very low or not detectable in the brain. The PDT efficacy of HA in the l iposome and DMSO saline systems was determined by evaluating the tumor volu me regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the h ighest retention of IIA in tumors. Similarly, the maximal PDT efficacy in D MSO saline was attained at 6 h postinjection, the highest IIA retention poi nt in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much hi gher than that of HA in DMSO saline and even hematoporphyrin monomethylethe r.