title: Superiority of N-methyl pyrrolidone over albumin with hypericin for fluorescence diagnosis of human bladder cancer cells implanted in the chick chorioallantoic membrane model.
abstract: Formulations of hypericin (HY) with plasma protein have been conventionally used, but to date, no alternative pharmaceutical formulation has been developed for clinical use. Previously, it was reported that formulation of HY containing a biocompatible solvent and penetration enhancer, N-methyl pyrrolidone (NMP) was found to be effective for the delivery of HY across in vivo chick chorioallantoic membrane (CAM). This present study reports further investigations on the HY-NMP formulations in CAM implanted with human bladder cancer cells as a potential fluorescence diagnostic agent of cancer. The conventional formulation of HY (HY-HSA 0.5%) was included as control. The red-to-blue (I(R)/I(B)) intensity ratio of fluorescence images was used as a diagnostic algorithm, to differentiate the uptake of HY between tumor and adjacent regions on CAM. Results indicated that HY-NMP 0.05% was significantly better than HY-HSA 0.5%. The findings of the I(R)/I(B) ratios between tumor and adjacent tissues, indicated the potential of using NMP as an alternative to plasma protein in clinical fluorescence diagnosis with HY. The NMP formulations investigated were able to produce significantly higher contrast for tumor tissues and at earlier time points than was possible with HY-HSA 0.5%.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Constance Lay Lay
authors.initials: CL
authors.lastname: Saw
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
authors.forename: William Wei Lim
authors.initials: WW
authors.lastname: Chin
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.forename: Paul Wan Sia
authors.initials: PW
authors.lastname: Heng
mesh_terms: D000818:Animals; D000873:Anthracenes; D045744:Cell Line, Tumor; D002470:Cell Survival; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism*; D003558:Cystoscopy; D005471:Fluoroscopy / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009368:Neoplasm Transplantation; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000737:chemistry / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D011760:Pyrrolidinones; D010569:Perylene; C004965:hypericin; C038678:N-methylpyrrolidone