Correlation of photosensitizer delivery to lipoproteins and efficacy in tumor and arthritis mouse models; comparison of lipid-based and Pluronic P123 formulations.
OBJECTIVE
The purpose of this study was the use of animal models to demonstrate the importance of drug delivery (verteporfin) to plasma lipoproteins in order to attain efficacy of photodynamic therapy (PDT) in vivo.


METHODS
Photosensitizers appropriately formulated in various vehicles such as pluronics and lipid-based systems were compared to delivery of the drug in DMSO in two in vivo systems. The first was a tumor model using male DBA/2 mice inoculated intradermally with M1 rhabdomyosarcoma cells and in the second, arthritis in the MRL -lpr mouse strain was enhanced by two intradermal injections of complete Freunds adjunct.


RESULTS
Those formulations in which the drug was in a monomeric form were better able to transfer drug to lipoproteins, which in turn led to superior PDT in vivo.


CONCLUSIONS
The ability to introduce drug in monomeric form into the circulation correlates well with efficacy of photosensitizer formulations in mouse arthritis and tumor models.
Chowdhary
Rubinah K
RK
Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
Sharif
Isha
I
Chansarkar
Namrata
N
Dolphin
David
D
Ratkay
Leslie
L
Delaney
Sean
S
Meadows
Howard
H
D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D010949:Plasma / Q000378:metabolism
D008074:Lipoproteins; D017319:Photosensitizing Agents