Quantification of the selective retention of palladium octabutoxynaphthalocyanine, a potential photothermal drug, in mouse tissues.
Palladium octabutoxynaphthalocyanine (PdNc(OBu)8) is a potential photothermal therapy (PTT) agent, absorbing strongly in the near-infrared region with no ability to induce photodynamic-type sensitisation (unlike many related napthalocyanines). We report here on the application of high pressure liquid chromatography (HPLC) with near-infrared absorption detection for the determination of the tissue accumulation and clearance of PdNc(OBu)8 in a tumour-bearing mouse model (Balb/c mice with EMT6 carcinoma tumour). Due to its insolubility in aqueous-based solvents, the drug was delivered intraperitoneally in a Cremophor-containing vehicle. Good selective accumulation of the drug into the tumour versus muscle or skin is observed, with the best combination of selectivity and tumour concentration occurring at 24-72 h after drug administration. Clearance times are quite long. Comparison with other similar drugs as reported in the literature indicates that the Cremophor-containing vehicle is likely in large part responsible for the observed pharmacokinetic behaviour. This drug shows potential for PTT and will be investigated further for therapy in this animal model.
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON.
M
M
Bucking
E F
EF
Gudgin Dickson
M
M
Farahani
F
F
Fischer
D
D
Holmes
G
G
Jori
J C
JC
Kennedy
M E
ME
Kenney
X
X
Peng
R H
RH
Pottier
G
G
Weagle
D000818:Animals; D005260:Female; D007211:Indoles / Q000493:pharmacokinetics; D054833:Isoindoles; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010165:Palladium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011092:Polyethylene Glycols; D014018:Tissue Distribution
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C428883:palladium 5,9,14,18,23,27,32,36-octabutoxynaphthalocyanine; C022131:cremophor; D011092:Polyethylene Glycols; D010165:Palladium; C013647:phthalocyanine