Transport of Hypericin across Chick Chorioallantoic Membrane and Photodynamic Therapy Vasculature Assessment

Abstract

Photodynamic therapy (PDT) utilizes a photosensitizer for the treatment of superficial cancers. Hypericin (HY; a naphthodianthrone, MW 504.45; Fig. 1) is a potent and promising photosensitizer found in the plant, Hypericum perforatum, commonly known as St. John's wort.1) HY exhibits a bright fluorescence with potent photosensitizing properties. It was reported to be useful for the detection of bladder carcinoma in situ, with a sensitivity and specificity of 94% and 95% respectively.2) Recent studies in our research group suggest that HY induces vascular damage and caused direct tumor cell death in human mucosal carcinoma cells with murine tumor models.3) St John's wort had been demonstrated to be an efficacious antidepressant of superior short-term safety profile when compared with other standard antidepressants 4) although concerns were raised over potential interactions between St. John's wort and certain other prescribed medicines.5) Topical application of HY in PDT will definitely reduce such concerns and allow drug delivery to the target site with reduced risk of systemic side effects. 2)HY is sparingly soluble in water. 6) Plasma protein was proposed as an 'effective' HY transporter/carrier 2) but an acceptable pharmaceutical solvent has still to be found for HY. Due to its hydrophobicity, dimethyl sulfoxide (DMSO) is a popular solvent for the preparation of HY in biodistribution studies [6][7][8] as well as to assess phototoxicity of HY. 9) However, these formulations are not ideal for actual clinical use in human. Recently, we have investigated the effectiveness of N-methyl pyrrolidone (NMP) as a potential solvent for HY in the chick chorioallantoic membrane (CAM) model for its potential anti-vasculature effects.10) This present study further investigated quantitatively the uptake of HY and PDT vascular damage on CAM. Also, the role of solvent system on HY transport will be examined.The chemical groups reported to cause the phototoxic effects of HY-PDT are the semiquinone, singlet oxygen and superoxide anion radicals. 11) Concomitantly, it was suggested that damage to the tumor vasculature is the primary mechanism of tumor destruction instead of direct tumor killing via apoptosis or necrosis.8) The CAM model had been used to evaluate photosensitizers' ability to induce vasculature damage.12) Other proposed uses of CAM include as an acceptable alternative to in vivo irritation tests on mucous membranes, 13) model tissue for surgical retinal research and simulation, 14) drug screening model for sensitizers in retinal disease, 15) short-term in vivo system for human skin 16) and in vivo test systems for human prostate cancer cells.17) The CAM assay will possibly enable a reduction or substitution of experiments on animals. It has several advantages including simplicity, rapidity, sensitivity, ease of performance and cost effectiveness. This study examined the transport of a photosensitizer (hypericin, HY) using the chick chorioallantoic membrane (CAM) as a model of transport after topical administration. Th...

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Evaluation of vascular effect of Photodynamic Therapy in chorioallantoic membrane using different photosensitizers

“…The chorioallantoic membrane of chicken eggs is known as CAM and is probably the most used in vivo model to study angiogenesis and compounds activities in vascular endothelium. With a direct access to blood vessels and embryo, this model is simple, cheap and of easy implementation in laboratory environment [15][16][17].…”