Drug release characteristics of lipid based benzoporphyrin derivative.
OBJECTIVE
The purpose of this study was to examine the transfer of verteporfin (BPDMA) from its lipid based formulation to serum proteins.


METHODS
As a result of BPDMA being confined to the lipid phase, it was found that fluorescence from the photosensitizer was highly concentration quenched. This phenomenon was used to demonstrate rapid transfer of lipid-based drug to various plasma components such as albumin and lipoproteins. Gel electrophoresis was used to show transfer of drug to lipoproteins.


RESULTS
Loss of fluorescence quenching showed rapid transfer of the drug from its lipid based formulation to serum proteins. Gel electrophoresis showed that both the drug and phospholipid components were transferred to the lipoprotein fraction concurrently. The electrophoretic mobility of plasma lipoproteins was increased as a result of their interaction with lipid-based BPDMA. It was also shown that the lipid-based structures were readily destabilized in the presence of relatively low concentrations of plasma, and that liposomes of this lipid composition were highly unlikely to be found intact in the circulation following intravenous injection.


CONCLUSIONS
Verteporfin is rapidly transferred from its lipid based formulation to serum proteins. This rapid transfer, particularly to lipoproteins, provides a mechanism for its rapid delivery to cells.
Chowdhary
Rubinah K
RK
Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
Shariff
Isha
I
Dolphin
David
D
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism*; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D004587:Electrophoresis, Agar Gel; D008055:Lipids / Q000737:chemistry; D011166:Porphyrins / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D000077362:Verteporfin
D000970:Antineoplastic Agents; D001798:Blood Proteins; D008055:Lipids; D011166:Porphyrins; D000077362:Verteporfin; D012710:Serum Albumin, Bovine