Correlation of Photosensitizer Delivery to Lipoproteins and Efficacy in Tumour and Arthritis Mouse Models; Comparison of Liposomal and Pluronic P123 Formulations
Chowdhary, R.K., Ratkay, L., Meadows, H., Sharif, I., Delaney, S., Chansarkar, N., and David Dolphin
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. Photosensitizers were 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. 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.