The potential application of chlorin e6-polyvinylpyrrolidone formulation in photodynamic therapy.
Much research has been focused on developing effective drug delivery systems for the preparation of chlorins as potential photosensitizers for PDT. This report describes the evaluation of a new water-soluble formulation of chlorin e6 consisting of a complex of trisodium salt chlorin e6 and polyvinylpyrrolidone (Ce6-PVP) for application in photodynamic therapy (PDT) with 2 specific aims: (i) to investigate its fluorescence kinetics in skin, normal and tumor tissue after intravenous administration, and (ii) to investigate its PDT efficacy. Our results demonstrate that this new formulation possesses photosensitizing properties with rapid accumulation in tumor tissue observed within 1 h after intravenous administration. Although high selectivity in tumor tissue was found between the period of 3 and 6 h, the efficacy of Ce6-PVP mediated PDT was best at 1 h drug-light interval. It is suggested that, the extent of tumor necrosis post PDT is dependent on the plasma concentration of Ce6-PVP, implying a vascular mediated cell death mechanism. A faster clearance rate of Ce6-PVP from the skin of nude mice was observed compared to Ce6. The new formulation of Ce6-PVP seems to show promise as an effective therapeutic agent.
Chin
William Wei Lim
WW
Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
Heng
Paul Wan Sia
PW
Bhuvaneswari
Ramaswamy
R
Lau
Weber Kam On
WK
Olivo
Malini
M
D000818:Animals; D002735:Chlorophyllides; D005453:Fluorescence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011205:Povidone / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D011205:Povidone