Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle.
C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.
Woodburn
K
K
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Chang
C K
CK
Lee
S
S
Henderson
B
B
Kessel
D
D
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D014677:Pharmaceutical Vehicles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
C089925:7,12-dioctyl-3,7,13,17-tetramethyl-8-porphinone-2,18-dipropionic acid; D001798:Blood Proteins; D014677:Pharmaceutical Vehicles; D017319:Photosensitizing Agents; D011166:Porphyrins